Marker Of Ischemia Research Articles

Therapeutic effect of Berberis vulgaris fruit extract on histopathological changes and oxidative stress markers of ovarian ischemia and reperfusion injury in rats

AimThis study aimed to investigate the possible protective effect of berberine, the active compound of Berberis vulgaris plant extract, which has anti-inflammatory and antioxidant properties, in an ovarian ischemia–reperfusion model by utilizing molecular, biochemical, and histopathological methods. MethodsIn this experimental study, 42 adolescent female Sprague Dawley rats (6 weeks old) were divided into 7 equal groups. Under anesthesia, ischemia was induced by ligating the bilateral adnexal tissues, and after 3 h of ischemia, reperfusion was achieved by removing the adnexal ligation. Berberis vulgaris extract was administered by oral gavage 1 h after ischemia for the ischemia groups and 1 h before reperfusion for the ischemia + reperfusion groups. After 3 h of reperfusion, the experiment was terminated. ResultsThe administration of Berberis vulgaris extract decreased the hemorrhagic areas, reduced the number of TUNEL-positive cells, and decreased CYC1 immunoreactivity levels in histopathological analysis compared to the groups subjected to ischemia or ischemia + reperfusion without the plant extract. CAT, SOD, and GSH increased due to Berberis vulgaris administration while MDA levels decreased. Berberis vulgaris also downregulated TNF-α levels compared to the ischemia and ischemia + reperfusion groups. ConclusionBerberis vulgaris extract may have a protective effect against ovarian ischemia–reperfusion injury. Further molecular studies are needed to clarify this protective effect.

Maternal Serum SCUBE-1: A Novel Ischemic Marker in Preeclampsia.

SCUBE-1 (Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-domain-containing protein 1) is a novel marker of ischemia, which is a cell surface-secreted protein in the platelets and endothelial cells. The aim of the study is to measure serum SCUBE-1 levels and investigate their association with uteroplacental blood flow in patients with preeclampsia. The study was conducted on patients with preeclampsia. Maternal serum SCUBE1 and IMA levels were the main outcomes. The control group consisted of gestational-age-matched pregnant women. Fetal umbilical artery (UA) pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio (CPR), and maternal uterine artery (UtA)-PI were also examined, and correlation analysis was performed to reveal the association between maternal serum SCUBE1 levels and Doppler findings. The study group consisted of thirty-two preeclamptic patients, and the control group consisted of thirty-two uncomplicated singleton pregnancies. Maternal serum SCUBE1 and IMA levels were significantly higher in preeclamptic women compared to the control group (p < 0.000, p < 0.004, respectively). Mean UtA-PI values and fetal UA-PI values were significantly higher in preeclamptic pregnant women compared to the control group (p < 0.05, p < 0.05, respectively). However, the average CPR was significantly lower in pregnant women with preeclampsia (p < 0.05). While no significant correlation was found between maternal serum SCUBE1 levels and UA-PI and CPR (p > 0.05, p > 0.05, respectively), a significant correlation was found between right and left UtA-PI (p < 0.004, p < 0.006, respectively). The maternal serum SCUBE1 level is increased in patients with preeclampsia, and this increase is significantly correlated with the maternal uterine artery pulsatility index.

AI derived myocardial left ventricular volumes outperforms clinician segmentation for prediction of all-cause mortality

Abstract Background Measuring heart structure and function drives much cardiac decision making and therapy. Precise quantification is therefore of high importance, but manual (clinician) segmentation introduces measurement variability. Purpose Automated segmentation of cardiac MRI (CMR) left ventricular (LV) volumes provides improved precision but how this translates into clinical outcomes has yet to be defined. In order to test predictive accuracy in a wide range of adverse LV morphologies, we applied AI LV segmentation to patients with coronary disease or cardiomyopathy. Methods Scans were analysed from a retrospective clinical CMR database and mortality data was obtained from a national database. Clinician measurement of indexed LV end-diastolic volume (LVEDVi), LV mass (LVMi), myocardial contraction fraction (MCF: ratio of stroke volume to myocardial volume; a measure of myocardial efficiency) and EF were recorded from clinical reports (all senior clinicians with &amp;gt;5 years level 3 experience) and compared to AI measurement using a segmentation algorithm. This has previously been shown to exceed human precision and required no manual correction (1,2). Random survival forests were built to identify overall predictive value of AI vs clinician derived LV volumes. These are machine-learning algorithms for predicting time-to-event outcomes and can capture complex relationships between predictors and outcome. Random survival forests were built from AI and clinician models with EF, EDVi, LVMi and MCF as predictors for all-cause mortality. A train:test (80:20) split, stratified for outcome was employed. Concordance (C)-indices (measuring predictive accuracy) and permutation importances (measuring significance of each predictor within the model) (Table) with 1000 bootstrapped 95% confidence intervals and p-values were derived. Results 8,299 patients were analysed. Patients were 60(51-70) years old and 37% female. 49% had coronary disease, 25% had DCM and 19% had HCM. At a median follow-up of 5.3 years (IQR 4.2-6.6 years) there were 1,384 deaths (17%). AI derived LV-parameter models had higher predictive accuracy than clinician derived models (C-Indices: 0.66±0.002 vs 0.65±0.005, p&amp;lt;0.001). A subgroup analysis of patients undergoing ischaemia testing for coronary disease was performed (n=3,560) and markers of ischaemia (positive vs negative) and infarction (non-viable vs viable) were included in the models. AI had a higher predictive accuracy compared to clinicians when including these additional predictors (C-Indices: 0.68±0.03 vs 0.63±0.01, p&amp;lt;0.001). Conclusion AI derived LV volumes outperforms clinicians in prediction of all-cause mortality reflecting improved precision. Improvements in predictive accuracy are likely to be clinically important when applied to populations and high-risk groups. Manual clinician segmentation should be superseded by clinician-supervised AI.

Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) measurement in the detection of significant CAD in acute chest pain patients triaged using the No Objective Testing (NOT) rule

Abstract Background After rule-out of MI in ED chest pain patients, uncertainty exists with respect to which remaining patients would benefit from objective functional/anatomical testing to detect potential underlying CAD. Using proteomics, we experimentally identified IGFBP-3 as a biomarker to assist this risk stratification and applied its measurement to &amp;gt;3,000 ED patients from 3 separate studies. Methods An isolated rat heart perfusate model coupled to mass spectrometry identified markers of cardiac ischemia. Human cardiac ischemia was carried out using cardiac exercise stress testing (EST, n=12). Temporal changes in IGFBP-3 during experimental MI were determined in patients undergoing septal alcohol ablation (SAA, n=12) and arterio-venous gradients of IGFBP-3 were determined from cases of proscribed cardiac catheterisation (CC, n=14). The ability of IGFBP-3 to assist clinical assessment (ROC analyses, logistic regression, C-statistic, pathways analyses) and ED risk assessment by the No Objective Testing (NOT) rule was carried out on samples from 3 prospectively recruited studies (SPACE, NZ, n=766; APACE, CH, n=1,056; FAST-TRAC, USA, n=1,230). Results IGFBP-3 identified by MS was present in perfusates of ischemic hearts only (n=3). In human cardiac EST, a delta of IGFBP-3 (∆IGFBP-3) between 0-150minutes was seen in positive ischemic tests, but not in controls (n=6 per group, p=0.026). In SAA patients, peripheral IGFBP-3 levels did not change over 24 hours (n=12, p=0.573) whereas in CC patients, significant extraction gradients of IGFBP-3 were seen across the heart and liver (p=0.013, n=14). In ED chest pain patients identified by the NOT rule (n=1,708), ΔIGFBP-3 between presentation and +2 hours (∆ IGFBP-3) was an independent logistic model predictor of unstable angina (n=123) alongside age, sex, cholesterol and Hx of CAD/MI. At 90% specificity, ∆IGFBP-3 improved the sensitivity of the model from 31% to 43%, the PPV 20% to 25% and the NPV from 94% to 95% (p=0.020). IGFBP-3 made a small improvement in "low risk" NOT rule patient identification (29% to 30%), but made a larger improvement to the ROC curve based identification in NOT rule patients for the finding of stenosis &amp;gt;70% on angiography (n=101, AUC clinical model = 0.682; model plus ∆ IGFBP-3 = 0.725, p=0.044). Pathways analyses (that included hs-TnT) in angiography patients (n=224) revealed ∆IGFBP-3 generated a 28% relative increase in low risk case identification (n=46 to 59). Conclusions IGFBP-3 is identified as a novel potential biomarker of cardiac ischemia, that is taken up/degraded across the heart and appears less responsive to complete infarction (MI). 0-2 hour changes in IGFBP-3 (∆ IGFBP-3) in patients identified as eligible for ED based NOT rule inclusion show promise as a useful tool to identify those with significant CAD, evidenced by the diagnosis of unstable angina, positive EST results or findings of 70% occlusion on angiography.

Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease.

Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. We aimed to elucidate the postoperative changes in EPVSs in adult patients with MMD, clinical and radiological factors affecting the number of EPVSs, and the degree of postoperative changes. We counted the EPVSs in the centrum semiovale in each hemisphere on a T2-weighted MRI performed before surgery. EPVSs were quantified 3months and 2years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs. This study included 120 hemispheres of 65 adults with MMD. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs. The number of EPVSs markedly decreased at 3months and 2years after surgery compared with that before surgery (P < 0.01). PCA involvement (P = 0.04) and CBF impairment (P = 0.02) were independent predictors of the regression of EPVSs after surgery. The number of EPVSs in the centrum semiovale was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization, especially in the hemispheres with PCA involvement and CBF impairment. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.

Hydrogel-Integrated Heart-on-a-Chip Platform for Assessment of Myocardial Ischemia Markers.

Organ-on-a-chip platform scans offer a controllable environment and a physiological similarity to mimic human pathophysiology. In this study, a single-channel PDMS microchip was fabricated, characterized, and optimized to obtain a heart-on-a-chip platform, which is integrated with a hydrogel scaffold suitable for cardiomyocyte growth inside its channel. Single-channel chips with a size of 20 × 12 mm and a channel height ranging from 60 to 100 μm were produced using photolithography and soft lithography techniques. A gelatin-embedded alginate network-based hydrogel was further augmented with 3% (v/v) collagen type I. Pore sizes were in the range of 74-153 μm for H9C2 implantation and biomimicry. The hydrogels are characterized both on PDMS surfaces and in capillaries. The primary feature distinguishing this study from previous microchip studies is that it mimics the cell microenvironment much better using different hydrogel formulations instead of creating a 2D cell culture by passing fluids, such as fibronectin, for cell adhesion. Instead of using complex microchip designs, the chip system we created intends to provide a physiologically relevant copy by using a 3D cell culture to its advantage and a simple, single-channel architecture. The microchip study was combined with cardiomyocytes to create the heart-on-a-chip system and tested under normoxic and hypoxic conditions to create a myocardial ischemia model inside this channel. As a result, this heart-on-a-chip platform was shown to be utilized for the detection of several small-size biomarkers such as adenosine, ADP, lactic acid, l-isoleucine, l-glutamic acid, and oxidized glutathione via LC-MS/MS from control conditions and a myocardial ischemia model. Cell-embedded and hydrogel matrix-supported versions of this heart-on-a-chip system were successfully prepared and shown to provide powerful outputs with myocardial ischemia markers. In light of this research, these outputs aim to develop simple and biologically effective organ-on-a-chip systems for future research.

Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions

Atherosclerotic coronary artery disease is a significant global health threat, impacting millions annually. Over time, plaque buildup narrows the coronary arteries, reducing blood flow to the heart muscle and resulting in myocardial ischemia. Timely diagnosis and intervention are crucial for restoring the blood flow to the heart muscle and preventing myocardial infarction. Given the limited availability of screening and diagnostic tests, the early diagnosis of myocardial ischemia remains challenging. While cardiac troponin is considered the gold standard for detecting myocardial injury, its effectiveness in identifying myocardial ischemia is limited. Ischemia-modified albumin (IMA) is a modified albumin variant that serves as a sensitive and early marker for ischemia. Despite extensive research on diagnostic applications of IMA as a biomarker for ischemia, significant gaps remain in understanding its formation, sensitive and specific detection, and precise clinical utility. This review aims to address these gaps by compiling literature on IMA discussing the latest findings on structure and formation, and detection methods. Further research is required to enhance understanding of the structure and formation of IMA, aiming to develop novel detection techniques or improve existing ones. However, currently, available sophisticated methods are associated with higher expenses and require specialized equipment and qualified personnel.

Intestinal protection by nitric oxide supply in the simulation of artificial blood circulation and circulatory arrest: an experimental study

Cardiac surgery is associated with high risks of complications, and these risks increase when it comes to aortic surgery because of the technical complexity of the surgeries, the use of cardiopulmonary bypass (CPB) and “circulatory arrest” (CA) that leads to ischemia-reperfusion damage. Abdominal complications in cardiovascular surgery are not the most common complications but are associated with high mortality. Protecting the gastrointestinal (GI) organs from ischemia-reperfusion injury is still a serious problem. According to a study of the organoprotective properties of nitric oxide (NO), its effectiveness in the treatment of diseases of the cardiovascular system, lungs, and kidneys has been proven, and observational results have shown that patients who were administered NO were less prone to complications from the gastrointestinal tract.The aim of the study was to evaluate the protective properties of NO for the intestines during simulated surgery under CPB and hypothermic CA. Methods. The study was conducted on sheep (n = 24). The animals were divided into 4 groups: the “CPB” group with the standard CPB protocol, the “CPB + NO” group with CPB and NO administration, the “CPB + CA” group with the standard CPB and CA protocol, and the group “CPB + CA + NO” with CPB and CA and NO administration. Instrumental and laboratory parameters were monitored at all stages of the experiment to assess the effectiveness and safety of CPB and CA simulation. In intestinal biopsy samples, the changes in the defecation rate, the concentration of a biochemical marker of intestinal ischemia (intestinal enterocyte fatty acid binding protein – i-FABP), and tissue concentrations of adenosine triphosphate (ATP) and lactate were assessed.Results. A higher rate of defecation was established (p = 0.046) in the “CPB + NO” group after CPB compared to the “CPB” group. The concentration of i-FABP in the CPB + NO group after CPB was lower compared to that in the CPB group (p = 0.002), and it was lower in the “CPB + CA + NO” group compared to the “CPB + CA” group (p = 0.033). 1 hour after CPB, the tissue concentration of ATP in intestinal biopsies in the “CPB + NO” group was higher than in the CPB group (p = 0.005).Conclusion. When modeling CPB and CA in the experiment, a positive effect of NO therapy on the intestine was noted: the functional state improved, the concentration of i-FABP decreased, and the concentration of ATP in intestinal biopsies increased.

Integrating rSO2 and EEG monitoring in cardiopulmonary resuscitation: A novel methodology

Despite improvements in cardiopulmonary resuscitation (CPR), survival and neurologic recovery after cardiac arrest remain poor due to ischemia and subsequent reperfusion injury. As the likelihood of survival and favorable neurologic outcome decreases with increasing severity of ischemia during CPR, developing methods to measure the magnitude of ischemia during resuscitation is critical for improving overall outcomes. Cerebral oximetry, which measures regional cerebral oxygen saturation (rSO2) by near‐infrared spectroscopy, has emerged as a potentially beneficial marker of cerebral ischemia during CPR. In numerous preclinical and clinical studies, higher rSO2during CPR has been associated with improved cardiac arrest survival and neurologic outcome. There is also emerging evidence that this can be integrated with electroencephalogram (EEG) monitoring to provide a bimodal system of brain monitoring during CPR. In this method’s review, we discuss the feasibility, application, and implications of this integrated monitoring approach, highlighting its significance for improving clinical outcomes in cardiac arrest management and guiding future research directions.

Pandemic effect on ischaemic burden and prehospital time in acute coronary syndrome

Background: Acute coronary syndrome (ACS) requires rapid identification and intervention. Early recognition of symptoms, detection of ischaemic markers in electrocardiograms (ECGs) and timely reperfusion therapy all reduce the total ischaemic time. In 2020, SARS-CoV-2 emerged as a new threat to people with cardiac disease: calls to emergency departments, emergency department visits and hospital admissions for acute cardiac conditions decreased, possibly because patients delayed seeking care because of fear of SARS-CoV-2 exposure. The hypothesis of this study was that patients presenting with ACS during the pandemic would have more ischaemic features and longer prehospital time intervals than those presenting before the pandemic. However, there were no significant differences between pre-pandemic and pandemic groups regarding incidence of ECG ischaemic markers, elevated troponin, adverse outcomes or prehospital time intervals. Non-ST-elevation myocardial infarction was significantly higher in the pandemic sample, which suggests that patients with less severe symptoms sought treatment during the pandemic.

Troponin efficacy in the diagnosis of acute coronary syndrome in patients with chronic renal failure.

There is no consensus on whether cardiac troponins with high reliability values should be different diagnostic criteria for acute myocardial infarction in patients with and without renal dysfunction. Although it is often emphasized that the etiology of elevated troponin levels in chronic kidney disease (CKD) remains unclear, elevated cardiac troponin (cTnT) levels have been associated with increased subclinical cardiac damage in these patient groups. In this study, we investigated the value of cTnT value in diagnosing acute coronary syndrome in CKD patients with high clinical suspicion of acute coronary syndrome and without acute ST segment elevation on electrocardiogram. The aim was to prevent cardiac ischemia from being overlooked in CKD patients. Coronary angiography revealed vessel occlusion in 192 patients, and the mortality rate after treatment decisions was 6.7%. The first measured troponin results showed a significant difference in patients who did not survive, indicating the prognostic value of troponin levels. Troponin values were compared with cardiovascular pathologies obtained by angiography, and elevated troponin levels strongly correlated with pathologic angiography results. The conclusion highlighted that despite prognostic uncertainties, biomarkers used for acute myocardial infarction diagnosis in patients with renal insufficiency are reliable in those with renal dysfunction. Elevated cTnT levels in CKD patients are considered a clear marker of cardiac ischemia, emphasizing the need for careful consideration of troponin values in this population.

Ischemia-Modified Albumin (IMA) Is Associated with Poor Survival in Patients with Newly Diagnosed Idiopathic Pulmonary Fibrosis (IPF): A Pilot Study.

There are increasing efforts to better predict adverse outcomes for idiopathic pulmonary fibrosis (IPF). Our aim was to assess the prognostic potential of ischemia-modified albumin (IMA), an established circulating marker of ischemia and, more recently, oxidative stress, in a cohort of 56 IPF patients recruited between 2015 and 2023 at the University of Sassari, Italy. Demographic and functional parameters and serum IMA concentrations were measured at baseline. Non-survivors had significantly higher IMA concentrations vs. survivors (508 ± 64 vs. 474 ± 42 mABSU, respectively; p = 0.035). The Kaplan-Meier analysis showed a significant association between higher IMA values and poor survival (HR: 3.32, 95% CI from 1.06 to 10.4, p = 0.039). In the Cox regression analysis, this association remained significant after adjusting for the force expiratory volume at 1 s, the total lung capacity, lymphocyte count, and pharmacological treatment (HR: 1.0154, 95% CI from 1.0035 to 1.0275, p = 0.01). IMA, an oxidative stress biomarker measurable using relatively simple and available methods, is independently associated with mortality in IPF. Therefore, its determination may enhance risk stratification and treatment decisions. Prospective studies involving larger cohorts are needed to confirm this association and to endorse the use of IMA in routine practice.

Prostaglandin E-major urinary metabolites as a new biomarker for acute mesenteric ischemia.

Acute mesenteric ischemia (AMI) is an emergent vascular disease caused by cessation of the blood supply to the small intestine. Despite advances in the diagnosis, intervention, and surgical procedures, AMI remains a life-threatening condition. Prostaglandin E2 major urinary metabolite (PGE-MUM), the urinary metabolite of prostaglandin E2, is known to be stable in urine and has been suggested to be a valuable biomarker for intestinal mucosal inflammation, such as ulcerative colitis. We therefore investigated whether or not PGE-MUM levels reflect the degree of ischemia in an intestinal ischemia-reperfusion model. Male rats were used to establish a superior mesenteric artery occlusion (SMAO) group, in which the superior mesenteric artery was clamped, and a sham group. The clamping times in the SMAO group were either 30 minutes or 60 minutes, and reperfusion times were either 3 hours or 6 hours, after which PGE-MUM values were measured. The histological injury score of the SMAO (30-minute ischemia and 6-hour reperfusion group, 1.8 ± 0.4; 60-minute ischemia and 6-hour reperfusion group, 4.7 ± 0.5) and were significantly greater than that of the sham group (0.4 ± 0.7, p < 0.05). The PGE-MUM levels in the SMAO group (30-minutes ischemia and 6-hour reperfusion group, 483 ± 256; 60-minutes ischemia and 6-hour reperfusion group, 889 ± 402 ng/mL) were significantly higher than in the sham group (30-minute and 6-hour observation group, 51 ± 20; 60-minute and 6-hour observation group, 73 ± 32 ng/mL; p < 0.05). Furthermore, the PGE-MUM value was corrected by the concentration of urinary creatinine (Cr). The PGE-MUM/urinary Cr levels in the SMAO group were also significantly higher than in the sham group ( p < 0.05). We found that intestinal ischemia-reperfusion increased urinary PGE-MUM levels depending on the ischemic time. This suggests the potential utility of PGE-MUM as a noninvasive marker of intestinal ischemia.

The Roles of Non-coding RNA Targeting Astrocytes in Cerebral Ischemia.

Astrocytes are key targets for treating cerebral ischemia in the central nervous system. Non-coding RNAs (ncRNAs) participate in the pathological processes of astrocytes in cerebral ischemia. Recent reports suggest that ncRNAs ameliorate the outcome of cerebral ischemia by mediating astrocytes' inflammatory reaction, oxidative stress, excitotoxicity, autophagy, and apoptosis. Reconstructing cellular systems might offer a promising strategy for treating cerebral ischemia. This review briefly discusses the potential of ncRNAs as drug targets and explores the molecular regulatory mechanisms through which ncRNAs target astrocytes in cerebral ischemia. It provides an overview of the current research, discusses ncRNAs' implications as clinical markers for cerebral ischemia, and anticipates that ongoing research on ncRNAs may contribute to novel therapeutic approaches for treating this condition.

Modern biochemical markers of acute mesenteric ischemia

To analyze modern literature data on biochemical markers of critical mesenteric ischemia. We analyzed the most promising, highly specific and sensitive biochemical markers of total and segmental intestinal damage following acute mesenteric ischemia. Analysis included domestic and foreign literature data between 2015 and 2023. We identified the most easy-to-use for any hospitals biochemical markers with at least 90% sensitivity and specificity for further practical research. Further prospective research will provide a new step in solving the problem of timely diagnosis of acute mesenteric circulatory disorders.

A Study of the Usefulness of Tissue Doppler Imaging for the Diagnosis of Coronary Artery Disease in Patients with Left Bundle Branch Block

Abstract Background: In patients with left bundle branch block (LBBB), the diagnosis of ischemia by noninvasive modalities is cumbersome. Most of them such as stress tests, nuclear imaging, and magnetic resonance imaging have limitations in the detection of ischemia in this subset. The postsystolic motion (PSM) during the isovolumetric relaxation period on tissue Doppler imaging (TDI) is a sensitive and specific marker of ischemia. We aimed to see whether the TDI parameters can detect coronary artery disease (CAD) in patients with LBBB. Materials and Methods: Patients with LBBB (n = 64) who underwent coronary angiography were divided into two groups. Group A (n = 30) included patients with left anterior descending (LAD) artery stenosis of ≥70%, and group B (n = 34) included patients without LAD stenosis. All patients underwent TDI and various myocardial tissue velocity parameters were analyzed to detect the presence of CAD. P &lt; 0.05 was considered significant. Results: The TDI of the mid-interventricular septum showed a higher delayed amplitude of PSM (&gt;100 ms after aortic valve closure), lower myocardial systolic (Sm), and early diastolic (Em) velocities, and a higher late diastolic (Am) velocity in group A when compared to group B (all were significant, P &lt; 0.0001). Both the ratios Sm/PSM and Em/Am were significantly lower in group A compared to group B (P &lt; 0.0001). On receiver operating characteristic curve analysis to predict the presence of significant LAD stenosis, the value of Sm/PSM ratio &lt;0.8 showed the best combination of sensitivity (78%) and specificity (96%) with an area under the curve of 0.936. Conclusion: TDI, a noninvasive imaging modality, is reliable and effective in identifying myocardial ischemia in patients with LBBB.

Peripheral blood diagnostic markers of chronic cerebral hypoperfusion.

To investigate the efficacy of ischemia-modified albumin (IMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), brain-derived neurotrophic factor (BDNF), and visinin-like protein-1 (VILIP-1) in diagnosing chronic cerebral hypoperfusion (CCH). This retrospective study included 84 patients with suspected chronic cerebral ischemia admitted to Sichuan Provincial People's Hospital between February 2021 and April 2022. Arterial spin labeling (ASL) imaging and biological examinations were performed. According to the ASL perfusion imaging patterns, the patients were divided into a CCH group (n = 55) and a non-CCH group (n = 29). Serum markers of the two groups were compared, and correlation analysis was conducted between ischemic marker levels and cerebral blood flow (CBF) in the ischemic region, as measured by ASL. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of each marker for diagnosing chronic cerebral ischemia. The Delong test was used to compare AUC size between groups. Compared to the non-CCH group, the CCH group exhibited higher IMA levels and lower BDNF concentrations (P < 0.05). However, VILIP-1 and Lp-PLA2 concentrations were not significantly different between the two groups (P > 0.05). Moreover, IMA and BDNF levels were not correlated with CBF in the hypoperfused area. ROC curve analysis demonstrated that the cut-off values of 24.2915 U/mL and 6.714 ng/L for IMA and BDNF achieved a sensitivity of 83.6% and 41.8% and a specificity of 62.1% and 93.1%, respectively. Lastly, the areas under the curve for IMA and BDNF were 0.738 (95% confidence interval [CI], 0.627-0.848) and 0.631 (95% CI, 0.512-0.751), respectively. IMA and BDNF may have clinical value in the diagnosis of CCH.

Long-term normothermic autoperfusion of the cardiopulmonary complex ex vivo as a method of effective graft conditioning: an experimental study

Objective: To compare the effectiveness of 6-hour normothermic autoperfusion of a heart graft ex vivo with pharmaco-cold preservation using Bretschneider's solution (Custodiol, Dr Franz Köhler Chemie GmbH, Bensheim, Germany).Methods: Landrace pigs weighing 50 ± 5 kg and aged 4–5 months (n = 10) were selected as a model for a series of acute experiments. Cardiopulmonary conditioning using autoperfusion was conducted for 6 hours on the experimental group (n = 5). On the other hand, the control group underwent a 6-hour pharmaco-cold preservation with Bretschneider solution to recover the heart's pumping function. Graft preservation effectiveness was evaluated by measuring hemodynamic parameters, heartbeat, and myocardial ischemia marker concentrations.Results: After reperfusion and isolation of the working cardiopulmonary complex, cardiac output was 0.63 [0.37; 0.8] L/min and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (P &lt; .05). The levels of CPK-MB, LDH, troponin-I, and lactate in the coronary sinus blood was significantly higher in the control group.Conclusion: The study demonstrated significant benefits of normothermic autoperfusion in maintaining the morphofunctional status of the donor heart compared to pharmaco-cold preservation using Bretschneider's solution for 6 hours of ex vivo graft conditioning. Received 16 July 2023. Revised 8 September 2023. Accepted 11 September 2023. Funding: The study was carried out within the framework of project No. 23-25-10013 (agreement No. 23-25-10013 dated April 20, 2023 with the Russian Science Foundation, agreement No. р-52 dated April 3, 2023 with the Ministry of Science and Innovation Policy of the Novosibirsk Region). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, I.S. ZykovData collection and analysis: M.O. Zhulkov, A.R. Tarkova, I.S. Zykov, A.G. Makaev, A.V. Protopopov, M.N. Murtazaliev, F.Yu. Kosimov, N.A. Karmadonova, Ya.M. Smirnov, E.E. Kliver, A.M. Volkov, H.A. Agaeva, D.A. SirotaStatistical analysis: M.O. ZhulkovDrafting the article: M.O. ZhulkovCritical revision of the article: M.O. Zhulkov, D.A. Sirota, I.S. ZykovFinal approval of the version to be published: M.O. Zhulkov, A.R. Tarkova, I.S. Zykov, A.G. Makaev, A.V. Protopopov, M.N. Murtazaliev, F.Yu. Kosimov, N.A. Karmadonova, Ya.M. Smirnov, E.E. Kliver, A.M. Volkov, H.A. Agaeva, D.A. Sirota

Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.

Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (p = 0.000), T2DM-CKD 7.08-6.04% (p = 0.000), PreD+CKD 5.66-4.98% (p = 0.014), and PreD-CKD 6.03-4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, p = 0.000) in the prediabetes group. Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.

Ischemia-induced alterations in the electrocardiogram of salmonid fish

Cardiovascular diseases such as coronary arteriosclerosis are widespread and constitute severe health and welfare problems for both farmed and wild salmonid fish. However, effective tools for rapid screening and analysing heart diseases in fish do not currently exist. Electrocardiogram (ECG) recordings are widely used for screening and diagnosing numerous cardiac pathologies in humans, but the use of ECG techniques to diagnose and characterize cardiac abnormalities in fish is still in its infancy. In this study, we induced myocardial ischemia in anaesthetized rainbow trout by surgical coronary artery ligation. Additionally, we experimentally manipulated the fish's heart rate and environmental oxygen availability by altering gill water flow and oxygen saturation (i.e., no flow, normoxic flow and hyperoxic flow), and analyzed changes in the ECG profile in detail. The main ECG abnormalities observed in fish with ligated coronaries in normoxia were atrioventricular blocks, prolonged QRS duration, reduced QRS amplitude and changes in the ST-segment such as the presence of early repolarization pattern. Furthermore, when gill water flow was stopped, fish exhibited pronounced hypoxic bradycardia, which alleviated all ECG abnormalities in coronary ligated fish. This is the first study to provide a detailed characterization of electrocardiographic markers of myocardial ischemia in fish. Our study shows that hypoxic bradycardia improves cardiac electrical conductivity, presumably by reducing mismatches in myocardial oxygen supply and demand. Yet, the importance of avoiding hypoxic bradycardia in experimental and biomedical studies on anaesthetized fish is highlighted as it can potentially lead to incorrect ECG interpretations.