Early Ischemia Research Articles

Clot Burden Score and Early Ischemia Predict Intracranial Hemorrhage following Endovascular Therapy.

Intracranial hemorrhage is a known complication following endovascular thrombectomy. The radiologic characteristics of a CT scan may assist with hemorrhage risk stratification. We assessed the radiologic predictors of intracranial hemorrhage following endovascular therapy using data from the INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) study. Patients undergoing endovascular therapy underwent baseline imaging, postprocedural angiography, and 24-hour follow-up imaging. The primary outcome was any intracranial hemorrhage observed on follow-up imaging. The secondary outcome was symptomatic hemorrhage. We assessed the relationship between hemorrhage occurrence and baseline patient characteristics, clinical course, and imaging factors: baseline ASPECTS, thrombus location, residual flow grade, collateralization, and clot burden score. Multivariable logistic regression with backward selection was used to adjust for relevant covariates. Of the 199 enrolled patients who met the inclusion criteria, 46 (23%) had an intracranial hemorrhage at 24 hours. On multivariable analysis, postprocedural hemorrhage was associated with pretreatment ASPECTS (OR, 1.56 per point lost; 95% CI, 1.12-2.15), clot burden score (OR, 1.19 per point lost; 95% CI, 1.03-1.38), and ICA thrombus location (OR, 3.10; 95% CI, 1.07-8.91). In post hoc analysis, clot burden scores of ≤3 (sensitivity, 41%; specificity, 82%; OR, 3.12; 95% CI, 1.36-7.15) and pretreatment ASPECTS ≤ 7 (sensitivity, 48%; specificity, 82%; OR, 3.17; 95% CI, 1.35-7.45) robustly predicted hemorrhage. Residual flow grade and collateralization were not associated with hemorrhage occurrence. Symptomatic hemorrhage was observed in 4 patients. Radiologic factors, early ischemia on CT, and increased CTA clot burden are associated with an increased risk of intracranial hemorrhage in patients undergoing endovascular therapy.

Increased Peripheral CD137 Expression in a Mouse Model of Permanent Focal Cerebral Ischemia.

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.

Abstract TMP62: Emergency Triage to Predict Collaterals in Acute Ischemic Stroke: Imaging Bests Clinical Factors in the STRATIS Registry

Background: Collateral grade is an established determinant of outcomes in acute ischemic stroke (AIS). The triage, workflow and therapeutic options for AIS may be tailored to collaterals and identifying key predictors of collateral status may therefore be crucial. We hypothesized that degree of collateral circulation prior to endovascular therapy in AIS may be predicted at the time of initial patient evaluation and triage. Methods: The STRATIS Registry showed that timelines, technical, and functional outcomes could be effectively attained in a large real-world cohort of endovascular therapy. Baseline clinical and imaging predictors of core lab adjudicated collateral grade (ASITN) by conventional angiography were determined, using multivariate modeling. Results: 586 STRATIS subjects (67.5 ± 15.2 years, 52.7% male) presenting with AIS at 147.4 ± 101.8 min from symptom onset (TFSO) and median NIHSS score 17.0 (range 8.0,30.0) were analyzed. Collateral grade was poor (ASITN 0-1) in 81, moderate (ASITN 2) in 297 and good (ASITN 3-4) in 208. Baseline stroke severity inversely correlated with collaterals (NIHSS per point, OR 0.946, 0.916-0.977, p=0.001), yet no clinical variables such as age, sex or co-morbidities were predictive of collateral status. Less severe ASPECTS at imaging triage (median 9, range 2-10) was associated with better collateral grade (ASITN 0-1, median 7 (2-10); ASITN 2, 8 (3-10); ASITN 3-4, 9 (5-10), p<0.001) and the strongest predictor of collaterals during triage (per point, OR 1.608, 1.399-1.849, p<0.001). Interestingly, the predictive nature of ASPECTS was not modified by TFSO (p=NS). Specific ASPECTS regions (all cortical M1-M6, but no subcortical) affected by early ischemia were also predictive of collateral grade. In particular, insular ASPECTS changes at imaging triage was the strongest predictor of collateral grade (ASITN 0-1, 53/66 (80.3%); ASITN 2, 139/258 (53.9%); ASITN 3-4, 41/194 (21.1%), p<0.001). Conclusions: Imaging, using only ASPECTS, during triage strongly predicts collateral grade, irrespective of time from symptom onset. Clinical variables, however, may not be used to accurately predict collaterals in the real-world practice of endovascular therapy.

MicroRNA-124 expression in the brains of rats during early cerebral ischemia and reperfusion injury is associated with cell apoptosis involving STAT3.

Cerebral ischemia and reperfusion injury is a cause of death and disability in adults. MicroRNA-124 possesses protective effects against apoptosis in cerebral ischemia and reperfusion. To provide insights into the diagnosis and treatment of cerebral ischemia and reperfusion injury, the dynamic changes of microRNA-124 expression during the early stage of cerebral ischemia and reperfusion injury in rats was investigated by quantitative polymerase chain reaction. To elucidate the association between the dynamic expression of microRNA-124 and apoptosis, the expression of proteins associated with apoptosis, including caspase-3, apoptosis regulator Bcl-2 (Bcl-2) and apoptosis regulator Bax (Bax) was analyzed by immunohistochemistry and western blot analyses. As signal transducer and activator of transcription 3 (STAT3) is involved in cell apoptosis and associated with Bcl-2, the protein expression of STAT3 and its active form, phosphorylated (p-)STAT3, were analyzed by western blot analysis. The expression of microRNA-124 increased and the maximum value appeared 12 h after reperfusion. Similarly, the expression of Bcl-2 also peaked 12 h after reperfusion, however the expression of caspase-3 and Bax continued to increase after the 12 h time point. These results indicate that the expression of microRNA-124 is closely associated with Bcl-2 and serves a protective role, inhibiting apoptosis. As the upstream regulator of Bcl-2, the expression of p-STAT3 was in accordance with Bcl-2 expression and peaked 12 h after reperfusion. By contrast, STAT3 was downregulated and the minimum level of STAT3 protein was reached 12 h after reperfusion. In summary, during the early stage of cerebral ischemia and reperfusion, the dynamic expression of microRNA-124 exhibited protective effects through the inhibition of apoptosis via anti-apoptotic proteins Bcl-2 and STAT3. Conversely, caspase-3 and Bax maintain apoptosis. The present study provides evidence to aid in the understanding of cerebral ischemia and reperfusion injury and develops methods of diagnosis and therapy of this condition.

Intestinal fatty acid binding protein (I-FABP) as a marker for acute intestinal ischemia

Background: Acute mesenteric ischemia accounts for around 0.1% of all hospital admission and less than 1% of emergency admissions. However, the presentation is varied, and diagnosis is obscure. The diagnosis of intestinal ischemia demands a high index of suspicion. The overall mortality associated with mesenteric ischemia is between 60% and 93% but rises acutely once bowel wall infarction has occurred. Early diagnosis of ischemia remains the key to reduce morbidity and mortality. I-FABP is a cytosolic protein present in epithelial cells of intestines and released upon ischemia or necrosis of bowel. Author estimated the levels of I-FABP in serum and established it as a marker for acute intestinal ischemia.Methods: 40 patients admitted to JSS Hospital with suspected acute intestinal ischemia were included in the study. Plasma concentrations were quantified using ELISA for fatty acid binding protein 2. Statistical methods were applied and sensitivity and specificity of serum I-FABP were determined. Confirmation of ischemia was by histopathological analysis of the resected bowel specimen.Results: 23 patients out of the 40 were diagnosed to have intestinal ischemia. Mean values of serum IFABP levels were significantly higher in patients diagnosed with intestinal ischemia (65.94pg/ml in the non-ischemic group vs 673.53pg/ml in the ischemic group P=0.0002). Cut off chosen in diagnosing intestinal ischemia in this study was 187.59pg/ml. Sensitivity was 95.7% and specificity 88%.Conclusions: Serum I-FABP can be used for the diagnosis for intestinal ischemia. It is specific and sensitive marker to detect early bowel ischemia.

Incidence, Predictors, and Outcomes of In-Hospital Percutaneous Coronary Intervention Following Coronary Artery Bypass Grafting

BackgroundPost-operative acute coronary ischemia is an uncommon complication of coronary artery bypass grafting (CABG). However, data on the incidence and outcomes of early coronary ischemia and in-hospital percutaneous coronary interventions (PCIs) after CABG are scarce. OBJECTIVESThe aim of this study was to assess the incidence, predictors, and outcomes of early (in-hospital) PCI following CABG. MethodsThis study utilized the National Inpatient Sample to select patients who underwent CABG between January 1, 2003, and December 31, 2014. Patients who had acute coronary ischemia requiring in-hospital PCI after CABG were compared with patients who did not need PCI. The primary endpoint was in-hospital mortality. Secondary endpoints were major complications, length-of-stay, and cost. Predictors of the need for post-CABG PCI were assessed in multivariate regression analyses. ResultsAmong the 554,987 studied patients, 24,503 (4.4%) had suspected acute coronary ischemia and underwent angiography post-operatively, of whom 14,323 had PCI. The majority (71.4%) of PCIs were performed within 24 h following CABG. Unadjusted in-hospital mortality was higher in patients who underwent PCI (5.1% vs. 2.7%; p < 0.001). The excess mortality persisted after multiple risk adjustments and sensitivity analyses. Patients who underwent post-CABG PCI had higher rates of strokes (2.1% vs. 1.6%; p < 0.001), acute kidney injury (16% vs. 12.3%; p < 0.001), and infectious complications. Post-CABG PCI was also associated with longer hospitalizations and a ∼50% increase in cost. Nonelective admissions and off-pump CABG were the strongest predictors of needing an in-hospital PCI following CABG. ConclusionsIn-hospital post-CABG PCI is uncommon but is associated with significantly increased morbidity, mortality, and cost. Further studies are needed to assess modifiable risk factors for early coronary compromise following CABG.

Jejunal obstruction due to ischemic stricture: an unusual presentation

Background: The most common causes of mechanical small bowel obstruction are postoperative adhesions and hernias. Other etiologies of small bowel obstruction include, diseases intrinsic to the wall of the small intestine, like tumors, strictures, intramural hematoma and processes that cause intraluminal obstruction like intussusception, gallstones, foreign bodies etc. Ischaemic enteritis is a rare etiology, reported only in about 0.1% of cases. Ischaemic strictures of the small bowel are a result of decreased blood supply to the small intestine. They require surgical intervention for their management.Methods: Author presented a 40 year-old diabetic female who presented with upper GI obstruction of 2month duration. Her history of illnesses included stroke, myocardial infarction and a transient episode of intestinal obstruction occurring simultaneously 3years ago. On investigations, she was found to have an occlusive distal jejunal stricture. Author studied the literature for the various management options and selected the most appropriate one for her.Results: Exploratory laparotomy with resection and end to end anastomosis of the jejunal segment was done. The histopathology of the segment revealed ischaemic enteritis with large vessel blockade causing stricture. The patient had an uneventful post op recovery and is asymptomatic two months since.Conclusions: Ischaemic enteritis results in small intestinal obstruction due to intestinal stenosis in its chronic phase. Diagnostic delay is due to the differential diagnoses and missing out on the transient phase of early ischemia.

Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection

The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK−MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10–20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2= 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI.

Ischemic Lesions in Acute and Subacute Perimesencephalic Subarachnoid Hemorrhage.

Perimesencephalic hemorrhage (PMH) is a subtype of nonaneurysmal subarachnoid hemorrhage (SAH). In patients with aneurysmal SAH, the occurrence of acute ischemic lesions is associated with severity and poor outcome. We investigated the frequency of ischemic lesions on DWI in patients with PMH and compared it with the frequency of ischemic lesions in patients with aneurysmal SAH. From a prospective cohort of 80 patients with acute spontaneous SAH, we included 15 patients with PMH and 39 patients with aneurysmal SAH who were matched on the basis of their clinical condition (World Federation of Neurological Societies grade 1 or 2). MRI was performed less than 72 hours after SAH, 8-10 days after SAH, or at both points in time. The number and distribution of lesions previously seen on DWI that were also seen on a second MRI examination were assessed. Nonparametric tests were used to compare groups. Early acute ischemic lesions (those identified < 72 hours after SAH) were found in 46.2% of patients with PMH and in 62.9% of patients with aneurysmal SAH. No significant differences in the number of acute ischemic lesions between groups were noted less than 72 hours after SAH (median, 0.5 lesion [interquartile range {IQR}, two lesions] in patients with PMH vs one lesion [IQR, three lesions] in patients with aneurysmal SAH [p = 0.48] or 8-10 days after SAH (median, 0.5 lesion [IQR, four lesions] in patients with PMH vs 1.5 lesions [IQR, three lesions] in patients with aneurysmal SAH [p = 0.26]). However, 58.3% of patients with aneurysmal SAH had new infarcts at 8-10 days, compared with 7.1% of patients with PMH. Patients with PMH had diffuse ischemic lesions, whereas patients with aneurysmal SAH in the anterior circulation had mainly supratentorial lesions. Early ischemic lesions appeared on DWI both in patients with PMH and in patients with aneurysmal SAH. The number of lesions increased during the time window for vasospasm, mainly in patients with aneurysmal SAH. Further studies are required to better understand the pathophysiologic mechanisms behind early ischemia in patients with PMH and their impact on prognosis.

Role of Diffusion-weighted Imaging in Detecting Early Ischemic Brain Injury Following Aneurysmal Subarachnoid Hemorrhage.

Background:Aneurysmal SAH is the significant cause of morbidity and mortality in stroke patients. Early brain injury and delayed cerebral ischemia are the two main responsible pathophysiologic processes. Cerebral ischemia needs to be detected early so that early aggressive therapy could be started. Although Diffusion weighted imaging (DWI) has often been utilized for the measurement of acute ischemic strokes, its role in the detection of early cerebral ischemia due to aneurysmal subarachnoid hemorrhage has not been extensively investigated. This study is being carried out to describe the role of DWI in detecting early ischemic brain injury and outcome after aneurysmal SAH.Aim:Efficacy of DWI in detecting ischemic injury and predicting outcome after aneurysmal SAH.Material and Methods:In this prospective study 44 consecutive patients who had aneurysmal SAH; admitted within 7 days of their ictus were included. Hunt and Hess grade on admission and modified Fisher grade of SAH were noted. Plain CT brain and MR DWI was done on day before surgery. Diffusion restriction on DWI was correlated with postoperative neurological deficit, postoperative CT finding and outcome of the patient at 1 month follow-up.Results:DWI revealed restricted diffusion in 12 patients, out of which 1 patient was having infarction in preoperative CT scan, 6 patients were having postoperative deficit in the form of disorientation, hemiparesis and aphasia, and all patients were having infarction in postoperative CT scan. When DWI findings were compared on the basis of postoperative neurological deficit, postoperative CT finding and modified Rankin outcome score at 1month follow-up, results were statistically significant.Conclusion:DWI shows cerebral ischemia much earlier than CT scan in cases of aneurysmal SAH. It has significant correlation with postoperative neurological status and outcome of the patient.

Could glucagon-like peptide-1 be a potential biomarker of early-stage intestinal ischemia?

Intestinal ischemia, also called mesenteric ischemia, is a severe gastrointestinal and vascular medical emergency caused by a sudden decrease of blood flow through the mesenteric vessels. It generates hypoperfusion of intestinal tissues and can rapidly progress to intestinal wall infarction, systemic inflammation or even death if not treated in time. The mortality of this condition is still considerably high despite all the medical advances of the past few years. This is partially due to the difficulty of diagnosing early stage mesenteric ischemia. Indeed, a speedy and correct diagnosis is decisive for suitable medical care. However, early symptoms are unspecific and conventional clinical markers are neither specific nor sensitive enough. In the last few years, significant clinical and preclinical efforts have been made to find biomarkers which could predict gastrointestinal damage before it becomes irreversible. Here, the gut-derived hormone glucagon-like peptide-1 (GLP-1) is described as a potential early biomarker of this severe condition. Indeed, GLP-1 plasma levels rise rapidly in both mice and humans with intestinal ischemia. This discovery could counter the cruel lack of clinical biomarkers available to diagnose and therefore manage intestinal ischemia efficiently in the early stages. GLP-1 could thus become part of a panel of biomarkers for intestinal ischemia and could help to reduce the associated high mortality rates.

Evaluation of Z-VAD-FMK as an anti-apoptotic drug to prevent granulosa cell apoptosis and follicular death after human ovarian tissue transplantation.

To evaluate the efficiency of ovarian tissue treatment with Z-VAD-FMK, a broad-spectrum caspase inhibitor, to prevent follicle loss induced by ischemia/reperfusion injury after transplantation. In vitro, granulosa cells were exposed to hypoxic conditions, reproducing early ischemia after ovarian tissue transplantation, and treated with Z-VAD-FMK (50μM). In vivo, cryopreserved human ovarian fragments (n = 39) were embedded in a collagen matrix containing or not Z-VAD-FMK (50μM) and xenotransplanted on SCID mice ovaries for 3days or 3weeks. In vitro, Z-VAD-FMK maintained the metabolic activity of granulosa cells, reduced HGL5 cell death, and decreased PARP cleavage. In vivo, no improvement of follicular pool and global tissue preservation was observed with Z-VAD-FMK in ovarian tissue recovered 3-days post-grafting. Conversely, after 3weeks of transplantation, the primary follicular density was higher in fragments treated with Z-VAD-FMK. This improvement was associated with a decreased percentage of apoptosis in the tissue. In situ administration of Z-VAD-FMK slightly improves primary follicular preservation and reduces global apoptosis after 3weeks of transplantation. Data presented herein will help to guide further researches towards a combined approach targeting multiple cell death pathways, angiogenesis stimulation, and follicular recruitment inhibition.

GW29-e0701 Cardiopulmonary exercise test predict early myocardial ischemia in patients with coronary slow flow

GW29-e0701 Cardiopulmonary exercise test predict early myocardial ischemia in patients with coronary slow flow

Immunobiochemical markers of the gematoentsefalitics barrier and autosensibilization at early forms chronic ischemia of the brain

Immunobiochemical markers of the gematoentsefalitics barrier and autosensibilization at early forms chronic ischemia of the brain

Accuracy and Reliability of Multiphase CTA Perfusion for Identifying Ischemic Core.

Acute stroke treatment requires simple, quick and accurate detection of early ischemic changes to facilitate treatment decisions guided by published selection criteria. The aim of this study was to determine the accuracy and reliability of multiphase computed tomography angiography (mCTA) perfusion hypoattenuation for detecting early severe ischemia. Non-contrast CT (NCCT), mCTA for regional leptomeningeal score (mCTA-rLMC), and mCTA perfusion lesion visibility (mCTA-arterial and mCTA-venous) were assessed blinded to clinical information in patients treated with endovascular therapy (EVT). The extent of early ischemia defined by regions of hypoattenuation was evaluated by the Alberta Stroke Program Early CT Score (ASPECTS). The ASPECTS scores were dichotomized based on the American Heart Association (AHA) guidelines for EVT selection, ASPECTS ≥6 vs. <6. The diagnostic accuracy was calculated by comparison to 24-h magnetic resonance imaging (MRI) or CT ASPECTS. Inter-observer reliability of NCCT and mCTA ASPECTS was evaluated. Machine learning models were used to predict the clinical follow-up outcome, e.g. National Institutes of Health Stroke scale (NIHSS) and modified Rankin scale (mRS) from baseline imaging data and patient information. A total of 89acute stroke patients (68 ± 15years of age) were analyzed (33TICI-0, 56TICI-2b or 3). Median baseline NIHSS was 17. The mCTA-venous had alarge effect on accurately identifying early ischemia when dichotomized for ASPECTS ≥6 vs <6 (likelihood ratio [LR+] > 10 vs. [LR-] < 0.29) compared to the moderate effect of NCCT ([LR+] = 6.7; [LR-] = 0.56) and mCTA-rLMC [(LR+ = 8.0; (LR-) = 0.83)]. The inter-observer reliability in mCTA-venous was almost perfect for all ASPECTS regions except the internal capsule. The machine learning support factor regression model identified mCTA-venous as the most important imaging covariate for predicting 24-h NIHSS and 90-day mRS. The assessment of mCTA-venous permits amore accurate detection of early ischemia than NCCT and mCTA-rLMC score and is predictive of clinical outcome. We would recommend the inclusion of mCTA perfusion lesion in future endovascular trials aiming at extending current AHA guidelines for EVT in stroke patients with low ASPECTS.

Impact of Comorbidities and Smoking on the Outcome in Aneurysmal Subarachnoid Hemorrhage

The intention of this observational study is to show the significant impact of comorbidities and smoking on the outcome in aneurysmal subarachnoid hemorrhage (SAH). During this observational study 203 cases of treatment of ruptured intracranial aneurysms were analyzed. We examined and classified prospectively the 12 month outcome according to the modified Rankin Scale (mRS) considering retrospectively a history of smoking and investigated prospectively the occurrence of early and delayed cerebral ischemia between 2012 and 2017. Using logistic regression methods, we revealed smoking (odds ratio 0.21; p = 0.0031) and hypertension (odds ratio 0.18; p = 0.0019) to be predictors for a good clinical outcome (mRS 0–2). Age (odds ratio 1.05; p = 0.0092), WFNS Grade (odds ratio 6.28; p < 0.0001), early cerebral ischemia (ECI) (odds ratio 10.06; p < 0.00032) and delayed cerebral ischemia (DCI) (odds ratio 4.03; p = 0.017) were detected as predictors for a poor clinical outcome. Significant associations of occurrence of death with hypertension (odds ratio 0.12; p < 0.0001), smoking (odds ratio 0.31; p = 0.048), WFNS grade (odds ratio 3.23; p < 0.0001) and age (odds ratio 1.09; p < 0.0001), but not with ECI (p = 0.29) and DCI (p = 0.62) were found. Smoking and hypertension seem to be predictors for a good clinical outcome after aneurysmal SAH.

Abstract 255: Mechanical Stretch is Not a Major Cause of Ectopic Activation During Early Stage Regional Ischemia in an Isolated Left-Ventricular Working Heart Model

Background: Acute regional ischemia is a leading cause of death. Ectopic beats may initiate ventricular arrhythmias in the first hour after coronary occlusion; however, the origin of these beats remains poorly understood. Some studies suggest that abnormal mechanical stretch at the ischemic border zone may contribute to the initiation of ectopy. If mechanical stretch plays a major role in triggering ectopic beats, we therefore expect: I , left ventricular working (LVW) hearts will have higher frequency of post-occlusion ectopic activity than non-beating (NB) hearts; II , in LVW hearts, ectopic beats will arise from ventricular sites undergoing mechanical stretch. Methods and Results: Isolated pig hearts were assigned to NB or LVW groups (8 per group) and prepared for Langendorff or LVW perfusion, respectively. Contraction of NB hearts was suppressed with 10 μM blebbistatin. Acute regional ischemia was induced by LAD occlusion. Using a newly developed optical mapping system, electrical activity and mechanical deformation were simultaneously recorded from 0 to 60 minutes after LAD occlusion. Mechanical stretch (positive strain in 2 principal directions) was observed in the ischemic and border zones of LVW but not NB hearts (Figure, Panel A). There was no significant difference in the number of ectopic events in LVW hearts compared to NB hearts (58±35 vs. 32±36, p=0.17). Of the 45 ectopic events that originated from the LV mapping region in LVW hearts, &lt;20% (6) were from sites that underwent mechanical stretch in the prior cardiac cycle (Figure, Panel B). Conclusion: Mechanical stretch does not play a major role in triggering ectopic beats in early acute regional ischemia in this model.

Targeting Innate Immune Cells and Regulated Cell Death in Early Hepatic Ischemia Reperfusion Injury

Targeting Innate Immune Cells and Regulated Cell Death in Early Hepatic Ischemia Reperfusion Injury

Sensitivity analysis of ST-segment epicardial potentials arising from changes in ischaemic region conductivities in early and late stage ischaemia

Although computational studies are increasingly used to gain insight into diseases such as myocardial ischaemia, there is still considerable uncertainty about the values for many of the parameters in these studies. This is particularly true for the bidomain conductivity values that are used in normal tissue and, even more so, in ischaemic tissue, when modelling ischaemia. In this work, we extended a previous study that used a half-ellipsoidal model and a realistic model to study subendocardial ischaemia during the ST segment, so that we could simulate both early and late stage ischaemia. We found that, for both stages of ischaemia, there was still the same connection between the degree of ischaemia and the development of features such as minima and maxima in the epicardial potential distribution (EPD), although the magnitudes of the potentials were very often less, which may be significant in terms of detecting them experimentally.Using uncertainty quantification associated with the ischaemic region conductivities, we also determined that the EPD features were sensitive to the ischaemic region extracellular normal and longitudinal conductivities during early stage ischaemia, whereas, during late stage ischaemia, the intracellular longitudinal conductivity was the most significant. However, since we again found that these effects were minor compared with the effects of fibre rotation angle and ischaemic depth, this might suggest that it is not necessary to use different conductivity values inside and outside the ischaemic region when modelling ST segment subendocardial ischaemia, unless the magnitudes of the potentials are an important part of the study.

High-sensitive cardiac troponin hs-TnT levels in sudden deaths related to atherosclerotic coronary artery disease

IntroductionIschemic heart disease (IHD) related to atherosclerotic coronary artery disease (CAD) is one of the most prevalent causes of death in Europe. Postmortem evaluation of IHD remains a challenge because of possible non-specific autopsy finding in some autopsy cases, especially in early myocardial ischemia. High-sensitive cardiac troponin T (hs-TnT) is used today in clinical practice as the “gold standard” to diagnose the myocardial ischemia, and might also be applied as an ancillary tool for post-mortem evaluation. PurposeThe goal of this study is to evaluate the diagnostic value of post-mortem serum hs-TnT assay in cases of sudden death related to IHD. We will also investigate the influence of cardiopulmonary resuscitation (CPR) attempts on post-mortem hs-TnT levels. MethodsThe hs-TnT values in serum were retrospectively analysed in 85 autopsy data. 52 cases with clinical history and morphological results suggesting cardiac ischemia were included in the study group (mean age 53.5; age range 34–75) and 33 cases in the control group (mean age 40.4; age range 15–69). The group’s statistical comparison was performed using logistic regression model. ResultsOur study showed a significant non-linear association between hs-TnT serum values and post-mortem diagnosis of sudden deaths related to IHD (p-value 0.005). The shape of the relationship is showing that the probability of death due to IHD increases quickly with a light level of hs-TnT (maximum around 90ng/L) then decreases slightly while remaining at high in values. No significant difference in the hs-TnT serum values was found between the CPR and the non-CPR cases (p-value 0.304). ConclusionThe measurement of hs-TnT serum values might be considered as an ancillary tool for the evaluation of death related to IHD, while taking necessary precautions in the interpretation of the results.