Tissue Reperfusion Research Articles

Extending the Time Window for Tenecteplase by Effective Reperfusion of Penumbral Tissue in Patients with Large Vessel Occlusion (ETERNAL-LVO): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial.

The benefit of tenecteplase in the treatment of large vessel occlusion (LVO) patients presenting within 24 hours of symptom onset remains unclear. To assess the effectiveness and safety of tenecteplase, compared to standard of care, in patients presenting within the first 24 hours of symptom onset with a LVO and target mismatch on perfusion CT. The "Extending the time window for Tenecteplase by Effective Reperfusion of peNumbrAL tissue in patients with Large Vessel Occlusion" (ETERNAL-LVO) trial is a prospective, randomized, open-label, blinded endpoint, phase 3, parallel-group, superiority trial with covariate-adjusted 1:1 randomization, and adaptive sample size re-estimation. Patients with an anterior circulation LVO stroke, who present within 24 hours of stroke onset or last known well with a target mismatch on CTP or MRI, will be randomized to tenecteplase (0.25 mg/kg) or standard of care (alteplase 0.90 mg/kg or conservative management at clinician discretion) prior to undergoing endovascular therapy. The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) of 0-1 (no disability) or return to baseline mRS at 3 months. Secondary and safety outcomes include the proportion of patients with a mRS of 0-2 at 3 months, an ordinal analysis of the mRS at 3 months, the proportion of patients with symptomatic intracerebral haemorrhage (sICH), the proportion of patients with death due to any cause, and the proportion of patients with mRS 5-6 at 3 months (severe disability or death). The ETERNAL-LVO trial will build upon the current evidence for tenecteplase in the >4.5-hour window. Specifically, this trial will evaluate tenecteplase in a patient population who have access to endovascular therapy but may incur delays to endovascular therapy commencement or require transfer from a primary to a comprehensive stroke center. ClincialTrials.gov: NCT04454788.

Recanalization Does Not Always Equate to Reperfusion: No-Reflow Phenomenon After Successful Thrombectomy.

Thrombectomy for acute large vessel occlusion is a well-established treatment for stroke prevention. However, futile recanalization cases, where no-reflow occurs despite successful recanalization, have been reported. This study aimed to assess cerebral hemodynamics immediately after thrombectomy and their relationship with clinical outcomes. We prospectively enrolled patients who underwent successful thrombectomy (modified Thrombolysis in Cerebral Infarction [TICI] ≥2b) for internal carotid artery or middle cerebral artery occlusions at Nagasaki University Hospital between January 2021 and December 2023. Preoperative magnetic resonance imaging was performed, followed by flat-panel computed tomography perfusion 30 minutes after recanalization. Areas with cerebral blood flow <45%, Tmax >6 seconds, and cerebral blood volume <34%, 38%, and 42% were analyzed, and hypoperfusion intensity ratio and cerebral blood volume index were calculated using Rapid ANGIO. We assessed the correlation of these parameters with infarct expansion, hemorrhagic transformation, and poor outcomes, defined as modified Rankin Scale scores of 4 to 6, at 3 months. A total of 65 cases were analyzed. Infarct expansion, defined as a decrease in Alberta Stroke Program Early CT Score, occurred in 23 cases (12/28 TICI 2b and 11/37 TICI 2c/3). No-reflow, defined as Tmax >6 seconds, was observed in 80% of cases (52/65), regardless of TICI grade. The infarct expansion group in TICI 2b had a significantly larger residual cerebral blood flow <45% area (32.9±30.4 versus 10.6±14.5 mL) and a lower cerebral blood volume index (0.71±0.2 versus 0.92±0.2). Cerebral blood flow <45% (r=-0.57; P<0.001) and cerebral blood volume <34% (r=-0.40; P=0.001), not Tmax >6 seconds, negatively correlated with postoperative Alberta Stroke Program Early CT Score. In logistic regression analysis, cerebral blood flow <45% was an independent predictor of poor outcomes (adjusted odds ratio, 1.05 [95% CI, 1.00-1.11]; P=0.039). No-reflow is common after thrombectomy, suggesting that successful recanalization does not always result in immediate tissue reperfusion. Hemodynamic impairment postthrombectomy may persist, highlighting the need for adjunctive treatments.

Ferroptosis: A key regulator and potential target for tissue injury.

The maintenance of iron homeostasis is essential for proper body function. A growing body of evidence suggests that iron imbalance is the common denominator in many tissue injuries, including acute, chronic, and reperfusion injuries. Ferroptosis, a novel form of programmed cell death due to metabolic abnormalities, has become increasingly recognized as an important process mediating the pathogenesis and progression of numerous tissue injuries, including cerebral, myocardial, lung, liver, kidney, and intestinal injuries. Therefore, a thorough understanding of the mechanisms involved in the regulation of ferroptosis might contribute to improvements in disease management. In this review, we summarize the importance of ferroptosis in various tissue injuries, discuss the potential targets of ferroptosis in the treatment of tissue injuries, and describe the current limitations and future directions of these novel treatment targets.

Penerapan Hydrogel dan Antimicrobial Dressing terhadap Penyembuhan Luka dan Sensasi Perifer pada Pasien Gangrene Pedis

Gangrene is one of Diabetes Mellitus (DM) complication causing tissue death in wound and decreased peripheral sensation. Priority management of gangrene is through tissue reperfusion and wound care with modern dressing to enhance healing and increase periphery circulation. This research aimed to report wound healing progress and peripheral sensation gangrene in a patient who was given hydrogel and antimicrobial dressing. Research design used a descriptive case study approach. Sample involved one inpatient in West Java regional public hospital who was diagnosed with gangrene, had necrotic wounds, and poor peripheral perfusion, currently treated with modern dressing hydrogel and antimicrobial dressing. The instrument used is Bates Jensen Wound Assessment Tools (BJWAT), lowest score shows significant wound healing progress. Decreasing wound healing score using BJWAT questionnaire from 41 to 29, peripheral sensation (+), and monofilament score from 0/9 to 5/9 after the intervention. Modern dressing improved wound healing and peripheral sensation in gangrene pedis patient. Thus, it is expected to examine effectiveness of hydrogel and antimicrobial dressings on healing scores and peripheral sensation in gangrene pedis patients more extensively.

CASE SERIES: EFFICACY OF THROMBOLYSIS USING INTRAVENOUS ALTEPLASE IN ACUTE ISCHEMIC STROKE WITH ONSET LESS THAN 6 HOURS (CODE STROKE)

Background: The gold standard therapy for acute ischemic stroke is timely reperfusion of ischemic brain tissue. Intravenous thrombolysis with tPA is the only proven medical therapy for acute ischemic stroke within 4.5 hours of symptom onset using intravenous alteplase at a dose of 0.9 mg per kilogram of body weight. Hemorrhagic transformation is one of the complications of thrombolytic therapy and East Asian population having a higher prevalence of cerebral hemorrhage. This study will examine several cases of ischemic stroke that were treated with thrombolysis using a standard dose (0.9 mg/kg) of intravenous alteplase in acute ischemic stroke with an onset of less than 6 hours in the Special Region of Yogyakarta, especially at the UGM Academic Hospital. Objective: To determine the efficacy of standard dose thrombolysis using intravenous alteplase (rTPA-recombinant tissue plasminogen activator) in acute ischemic stroke with an onset of less than 6 hours through activation of the Code Stroke. Methods: Descriptive research design using a case series, the hyperacute stroke patients with an onset of less than 6 hours who received intravenous alteplase which were then assessed by the National Institutes of Health Stroke Scale (NIHSS) score at initial admission, 24 hours post-alteplase and 30 days post -alteplase. The study took place and was conducted from May to October 2022 by administering intravenous alteplase at a dose of 0.9 mg/kg body weight in acute ischemic stroke patients at UGM RSA who are eligible for thrombolysis therapy with a maximum administration time of 6 hours after stroke onset with the maximum dose of alteplase is 50 mg. Results: The study sample was 8 patients with acute ischemic stroke who were treated between May to October 2022. There were 2 patients who died before completing the 3-month follow-up. One of the patients died within the second week of treatment from sepsis which may have occurred from a pre-existing pneumonia. Another patient died from ileus that occurred 1 month after tissue plasminogen activator (tPA). However, the patient with this ileus showed clinical improvement at the 24-hour post-tPA follow-up, i.e. the initial NIHSS score of 12 improved to an NIHSS score of 6. Conclusion: The modified Alteplase dose, which is 0.9 mg/kg body weight with a maximum dose of 50 mg, at the onset of stroke less than 6 hours can be an option to maximize thrombolytic therapy while still considering the efficiency of treatment costs.

Novel roles of κ-opioid receptor in myocardial ischemia-reperfusion injury.

Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible damage to the myocardium. The number of mitochondria in cardiomyocytes is large, which generate adenosine triphosphate (ATP) to sustain proper cardiac contractile function, and mitochondrial dysfunction plays a crucial role in cell death during myocardial ischemia-reperfusion, leading to an increasing number of studies investigating the impact of mitochondria on ischemia-reperfusion injury. The disarray of mitochondrial dynamics, excessive Ca2+ accumulation, activation of mitochondrial permeable transition pores, swelling of mitochondria, ultimately the death of cardiomyocyte are the consequences of ischemia-reperfusion injury. κ-opioid receptors can alleviate mitochondrial dysfunction, regulate mitochondrial dynamics, mitigate myocardial ischemia-reperfusion injury, exert protective effects on myocardium. The mechanism of κ-OR activation during myocardial ischemia-reperfusion to regulate mitochondrial dynamics and reduce myocardial ischemia-reperfusion injury will be discussed, so as to provide theoretical basis for the protection of ischemic myocardium.

PNA5, a Novel Glycosylated Angiotensin 1-7 Treatment Improves Infarct Size and Fibrotic Remodeling in Ischemic Reperfusion Injury

Background: Reperfusion during an acute ischemic event is of paramount importance to rescue cardiac tissue. Paradoxically, reperfusion of the ischemic tissue promotes further cardiac injury. Increased reactive oxidative species (ROS) and inflammation contribute to ischemic reperfusion injury (IR). PNA5, a glycosylated analog of angiotensin-(1-7), decreases ROS and inflammation. The purpose of this study is to indicate if PNA5 treatment has the ability to reduce infarct (IN) size and improve cardiac remodeling in IR. We hypothesize that PNA5 will improve fibrosis and diminish IN size in IR. Methods: 3-month-old male mice (C57BI/6J) underwent IR surgery. Mice were anesthetized and the left anterior descending artery was litigated for 45 minutes. Ischemic areas were then reperfused. Mice were immediately injected with PNA5 (subcutaneously s.c. at 100μg/kg, n=11) or with saline as control (n=11). Injections were continued daily with PNA5 or saline for 8-weeks. At the end of treatment, mice were sacrificed. Upon sacrifice, hearts were re-ligated and perfused with Evans Blue to identify the areas at risk (AAR). Hearts were stained with 2-3-4-triphenyltetrazolium chloride to show IN area. IN size and AAR were determined using Image J. Paraffn-embedded hearts were stained with Picrosirius Red for fibrosis. Fibrosis was measured as a ratio of collagen to total tissue area for 17 regions in the left ventricle (LV). Values are represented as mean ± standard error of mean. Results: PNA5-treated mice IN size was significantly decreased compared to saline-treated mice. (IN/AAR: IR-Saline 0.17± 0.02; PNA5 0.10± 0.01, p=0.005; IN/LV: IR-Saline 0.08± 0.01; PNA5 0.05±0.01; p=0.002, student’s T-test). PNA5 reduced fibrosis in the LV compared to IR-saline mice Conclusions: These results indicate PNA5 as a potential therapeutic treatment for IR as it improves IN size and fibrotic remodeling in IR. [Formula: see text] Supported by NIA U01AG066623 to MH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Integrated bioinformatics analysis of retinal ischemia/reperfusion injury in rats with potential key genes.

The tissue damage caused by transient ischemic injury is an essential component of the pathogenesis of retinal ischemia, which mainly hinges on the degree and duration of interruption of the blood supply and the subsequent damage caused by tissue reperfusion. Some research indicated that the retinal injury induced by ischemia-reperfusion (I/R) was related to reperfusion time.In this study, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model group and at different reperfusion time (24h, 72h, and 7d) with the aid of whole transcriptome sequencing technology, and the trend changes in time-varying mRNA, lncRNA, circRNA were obtained by chronological analysis. Then, candidate circRNAs, lncRNAs, and mRNAs were obtained as the intersection of differentially expression genes and trend change genes. Importance scores of the genes selected the key genes whose expression changed with the increase of reperfusion time. Also, the characteristic differentially expressed genes specific to the reperfusion time were analyzed, key genes specific to reperfusion time were selected to show the change in biological process with the increase of reperfusion time.As a result, 316 candidate mRNAs, 137 candidate lncRNAs, and 31 candidate circRNAs were obtained by the intersection of differentially expressed mRNAs, lncRNAs, and circRNAs with trend mRNAs, trend lncRNAs and trend circRNAs, 5 key genes (Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa) were selected by importance scores of the genes. The result of GSEA showed that key genes were found to play vital roles in antigen processing and presentation, regulation of the actin cytoskeleton, and the ribosome. A network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 34 miRNAs and 48 lncRNAs, and 81 regulatory relationship axes, and a network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 9 miRNAs and 3 circRNAs (circRNA_10572, circRNA_03219, circRNA_11359) and 12 regulatory relationship axes were constructed, the subcellular location, transcription factors, signaling network, targeted drugs and relationship to eye diseases of key genes were predicted. 1370 characteristic differentially expressed mRNAs (spec_24h mRNA), 558 characteristic differentially expressed mRNAs (spec_72h mRNA), and 92 characteristic differentially expressed mRNAs (spec_7d mRNA) were found, and their key genes and regulation networks were analyzed.In summary, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model groups and at different reperfusion time (24h, 72h, and 7d). 5 key genes, Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa, were selected. Key genes specific to reperfusion time were selected to show the change in biological process with the increased reperfusion time. These results provided theoretical support and a reference basis for the clinical treatment.

A single-chain antibody construct with specificity of a natural IgM antibody reduces hepatic ischemia reperfusion injury in mice.

Natural immunoglobulin M (IgM) antibodies have been shown to recognize post-ischemic neoepitopes following reperfusion of tissues and to activate complement. Specifically, IgM antibodies and complement have been shown to drive hepatic ischemia reperfusion injury (IRI). Herein, we investigate the therapeutic effect of C2 scFv (single-chain antibody construct with specificity of a natural IgM antibody) on hepatic IRI in C57BL/6 mice. Compared with PBS-treated mice, C2 scFv-treated mice displayed almost no necrotic areas, significant reduction in serum ALT, AST and LDH levels, and significantly reduced in the number of TUNEL positive cells. Moreover, C2 scFv-treated mice exhibited a notable reduction in inflammatory cells after hepatic IRI than PBS-treated mice. The serum IL-6, IL-1β, TNF-α and MPC-1 levels were also severely suppressed by C2 scFv. Interestingly, C2 scFv reconstituted hepatic inflammation and IRI in Rag1-/- mice. We found that C2 scFv promoted hepatic cell death and increased inflammatory cytokines and infiltration of inflammatory cells after hepatic IRI in Rag1-/- mice. In addition, IgM and complement 3d (C3d) were deposited in WT mice and in Rag1-/- mice reconstituted with C2 scFv, indicating that C2 scFv can affect IgM binding and complement activation and reconstitute hepatic IRI. C3d expression was significantly lower in C57BL/6 mice treated with C2 scFv compared to PBS, indicating that excessive exogenous C2 scFv inhibited complement activation. These data suggest that C2 scFv alleviates hepatic IRI by blocking complement activation, and treatment with C2 scFv may be a promising therapy for hepatic IRI.

FGF-21: a novel biomarker predicting no-reflow in ST-segment elevation myocardial infarction.

Primary percutaneous coronary intervention (pPCI) is the most effective reperfusion therapy in the treatment of ST-elevation myocardial infarction (STEMI). Although the infarct-related artery of STEMI patients is effectively revascularized during pPCI, effective reperfusion in the myocardial tissue may not be achieved. This condition is called the no-reflow (NR) phenomenon. FGF-21 is a circulating hormone-like molecule primarily secreted by the liver and has been proven to be the main metabolic regulator of glucolipid metabolism and insulin sensitivity. The aim of this study was to investigate the predictive effect of FGF-21 on the development of the NR phenomenon in STEMI patients undergoing pPCI. This study included 91 patients with acute STEMI who underwent pPCI and 45 healthy participants. Patients with acute STEMI were split into two groups: 46 patients in the NR phenomenon group and 45 patients in the non-NR phenomenon group. Serum levels of FGF-21 were measured in all study groups. Serum FGF-21, white blood cell count, and high-sensitivity C-reactive protein (hs-CRP) values were considerably different amongst the groups (p = 0.001, p = 0.001, and p = 0.003, respectively). In comparison to patients without NR and the control group, STEMI patients with NR had considerably higher FGF-21 levels. In addition, the FGF-21 level of STEMI patients without NR was significantly higher than that of the control group. In multivariate logistic regression analysis, hs-CRP [odds ratio (OR) 2.106% 95% confidence interval (CI) (0.002-0.069) p = 0.038], age [OR 2.147; 95% (CI) (0.001-0.015); p = 0.0035], and serum FGF-21 levels [OR 4.644; 95% CI (0.003-0.006); p < 0.001] were independent predictors of NR formation. For FGF-21 ≥ 92.2 pg/Ml, 87% sensitivity and 88% specificity were found in predicting NR formation (area under the curve: 0.897, 95% CI: 0.841-0.954; p < 0.001). Our study demonstrates a strong association between the NR phenomenon, a key indicator of poor prognosis in acute STEMI patients, and an elevated FGF-21 level. These findings indicate FGF-21 as a novel and potent predictor of NR development in STEMI patients.

Stem Cells and Exosomes in Myocardial Ischemia-Reperfusion Injury: A Comprehensive Review of the Literature

Ischemia-reperfusion injury (IRI) remains a global public health problem, with increasing incidence which is associated with significant morbidity and mortality. The duration of blood flow deprivation is a critical risk factor in conditions such as myocardial infarction (MI), stroke, solid organ transplantation, and hemorrhagic shock. From a pathophysiological perspective, IRI leads to numerous architectural, cellular, and metabolic changes in tissues. Moreover, local and systemic inflammation occurs after reperfusion of ischemic tissue. Clinically, the treatment of cases with IRI is frequently restricted to supportive maneuvers, with no exact target-oriented therapies validated so far. Recent research reveals the efficacy of stem cells as a promising therapeutic approach. Additionally, exosomes have been suggested to exert a significant impact on the stimulation of useful signaling pathways in different cardiovascular diseases. This review provided an overview of the new treatment strategies such as stem cell therapy (SCT) and exosome-based treatments for improving myocardial IRI.

Use of thrombolytic therapy for treatment of stroke with ischemic type within the standard therapeutic window

The study focuses on stroke, the second leading cause of death worldwide. It specifically addresses the ischemic type of stroke, which constitutes the majority of cases globally and in Ukraine, driving the search for innovative and effective diagnostic and treatment strategies. Among these, reperfusion of brain tissue within the first hours of the disease can prevent irreversible brain damage or minimize its extent, thus reducing the degree of residual neurological deficit. Objective — to compare the outcomes between standard therapy and thrombolytic therapy (TT) in treating ischemic stroke, evaluating the efficacy of TT within the standard therapeutic window to optimize patient care. Materials and methods. The study was conducted in the Neurological Department No. 2 of Kyiv City Clinical Hospital No. 4 from July to December 2023. A total of 247 cases of ischemic type stroke were analyzed. 69 patients who were admitted within the standard therapeutic window were selected. They were divided into two groups. The experimental group included 42 patients aged between 42 and 89 years (average age — (71.0 ± 17.8) years) without contraindications, who agreed (themselves or through relative’s consent) to undergo TT. Alteplase was administered intravenously at a dose of 0.9 mg/kg body weight, 10 % of the dose as a bolus (over 1 minute), and 90 % within one hour. The control group consisted of 27 patients aged between 47 and 88 years (average age — (76.11 ± 8.9) years), who had contraindications for TT. They received standard therapy. Evaluations were conducted using the modified Rankin Scale, which allows for assessing the level of disability or dependence on external assistance in patients’ daily lives after a stroke. Results. The study demonstrated that TLT significantly improves the functional status of patients compared to standard therapy, as evidenced by a decrease in the level of disability to 0—1 points on the modified Rankin Scale at discharge from the hospital: in the control group — in 3 (11.1 %) patients, in the experimental group — in 16 (35.7 %, p = 0.047), i. e. the use of TLT significantly improved the functional status of more patients. In the experimental group, 4 patients died (9.5 %), in the control group — 5 (18.5 %). Conclusions. TLT effectively promotes the restoration of neurological functions and reduces the level of disability in patients with ischaemic cerebral stroke, which opens up prospects for further research. The results obtained indicate the need for wider use of TLT in clinical practice, taking into account individual patient risks and contraindications.

Erucin, a natural isothiocyanate, exerts pro-angiogenic properties in cultured endothelial cells and reverts angiogenic impairment induced by high glucose.

Insufficient vessel maintenance adversely impacts patients in terms of tissue reperfusion following stroke or myocardial infarction, as well as during wound healing. Angiogenesis impairment is a feature typical of metabolic disorders acting at the cardiovascular level, such as diabetes. Therapeutic angiogenesis regulation offers promising clinical implications, and natural compounds as pro-angiogenic nutraceuticals hold valuable applications in regenerative medicine. By using cultured endothelial cells from human umbilical veins (HUVEC) we studied functional and molecular responses following exposure to erucin, a natural isothiocyanate derived from Brassicaceae plants and extracted from the seeds of rocket. Erucin (at nanomolar concentrations) promotes cell migration and tube formation, similar to vascular endothelial growth factor (VEGF), through mobilizing paxillin at endothelial edges. At the molecular level, erucin induces signaling pathways typical of angiogenesis activation, namely Ras, PI3K/AKT, and ERK1/2, leading to VEGF expression and triggering its autocrine production, as pharmacological inhibition of soluble VEGF and VEGFR2 dampens endothelial functions. Furthermore, erucin, alone and together with VEGF, preserves endothelial angiogenic functions under pathological conditions, such as those induced in HUVEC by high glucose (HG) exposure. Erucin emerges as a compelling candidate for therapeutic revascularization applications, showcasing promising prospects for natural compounds in regenerative medicine, particularly in addressing angiogenesis-related disorders.

Systemic biomarker associated with poor outcome after futile reperfusion.

Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

Culprit Lesion Vessel Size and Risk of Reperfusion Injury in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study.

Microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) are well-established imaging biomarkers of failed myocardial tissue reperfusion in patients with ST-segment elevation-myocardial infarction treated with percutaneous coronary intervention. MVO and IMH are associated with an increased risk of adverse outcome independent of infarct size, but whether the size of the culprit lesion vessel plays a role in the occurrence and severity of reperfusion injury is currently unknown. This study aimed to evaluate the association between culprit lesion vessel size and the occurrence and severity of reperfusion injury as determined by cardiac magnetic resonance imaging. Patients (n=516) with first-time ST-segment-elevation myocardial infarction underwent evaluation with cardiac magnetic resonance at 4 (3-5) days after infarction. MVO was assessed with late gadolinium enhancement imaging and IMH with T2* mapping. Vessel dimensions were determined using catheter-based reference. Median culprit lesion vessel size was 3.1 (2.7-3.6) mm. MVO and IMH were found in 299 (58%) and 182 (35%) patients. Culprit lesion vessel size was associated with body surface area, diabetes, total ischemic time, postinterventional thrombolysis in myocardial infarction flow, and infarct size. There was no association between vessel size and MVO or IMH in univariable and multivariable analysis (P>0.05). These findings were consistent across patient subgroups with left anterior descending artery and non-left anterior descending artery infarctions and those with thrombolysis in myocardial infarction 3 flow post-percutaneous coronary intervention. Comprehensive characterization of myocardial tissue reperfusion injury by cardiac magnetic resonance revealed no association between culprit lesion vessel size and the occurrence of MVO and IMH in patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction.

Value of Immediate Flat Panel Perfusion Imaging after Endovascular Therapy (AFTERMATH): A Proof of Concept Study.

Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status. This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI (n = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4). Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26). FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite.

Intravenous Thrombolysis before Complete Angiographic Reperfusion: Beyond Angiographic Assessment to Target Microvascular Obstruction?

Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.

Inflammatory biomarker concentrations in dogs with gastric dilatation volvulus with and without 24-h intravenous lidocaine.

Canine gastric dilatation volvulus (GDV) is characterized by tissue ischemia, reperfusion, and systemic inflammation. Evidence exists that lidocaine exerts anti-inflammatory properties and potentially improves outcome. Prospective, randomized observational cohort study in client-owned dogs with GDV. The primary objective of the study was the determination of pro- and anti-inflammatory biomarker concentrations in dogs with GDV with and without intravenous (IV) lidocaine therapy. The second objective was the evaluation of side effects of lidocaine. Of 35 dogs included in the study, 20 dogs were assigned to receive lidocaine (LIDO) (2 mg/kg initially, followed by a continuous infusion at a rate of 50 μg/kg/min over 24 h) and 15 dogs not to receive lidocaine (NO-LIDO). Plasma concentrations of cytokines interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma, keratinocyte chemotactic-like, monocyte chemotactic protein, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, T0), immediately after surgery (T1), at 24 h (T24), and at 48 h (T48) post-surgery. No significant differences in concentrations of any cytokines were found between the LIDO- and the NO-LIDO group. Significant lower CRP concentrations (median [range]) were found in dogs with lidocaine compared to dogs without at T24 (97.5 pg/mL [46.3-161.7] vs. 127.9 pg/mL [26.9-182.0]; p = 0.046) and T48 (73.7 pg/mL [18.4-169.4] vs. 116.3 pg/mL [71.4-176.8]; p = 0.002). Dogs receiving lidocaine exhibited significantly impaired mentation, a prolonged period of anorexia, and longer hospitalization compared to dogs without lidocaine. Lidocaine administration had no impact on the plasma levels of cytokines during the 48-h study period, but significantly lower CRP concentrations were found at T24 and T48. Lidocaine's potential side effects require careful decision making regarding its use.

Abstract 15087: First Clinical Trial in China to Evaluate the Efficacy and Safety of Moyoassist® Extra-VAD System

Cardiogenic shock(CS)is associated with significant morbidity and mortality. For patients unresponsive to medicinal treatment, an alternative is a mechanical circulatory support (MCS) system. In China, common treatments using short-term MCS include IABP and VA-ECMO, both methods found their limitations. Therefore, a better strategy must be proposed to improve prognosis in CS patients, such as extracorporeal VAD (Extra VAD). Here, we reported 40 patients' data collected from a prospective, multicenter, single group clinical trial conducted from July 2021 to Feb 2023, which aims to evaluate the efficacy and safety of MoyoAssist® Extra-VAD system. MoyoAssist® is developed based on fully magnetically levitated pump technology to temporarily support the left, right, or biventricular circulation of patients with acute heart failure and cardiogenic shock of all causes. Patients were recruited for various indications, with PCCS (50%) and BTT (32.5%) being the top two causes. A combination of median sternotomy (22.5%), peripheral venous cannulation (52.5%) and mini-incision (25%) were employed to implant the device. Especially, jugular vein cannulation was a pioneering approach proposed to enable patients’ early ambulation and recovery. MoyoAssist® Extra-VAD has demonstrated stable and sufficient circulation support without severe device associated adverse events. The mean support duration was 7d16hrs, and overall survival rate at 30-day follow up was 62.5%. Hemodynamics indicated improvement with increased MAP and reduced CVP in all sub-groups. Lactate has shown a significant decrease in the PCCS-survival group (3.95 vs. 1.05, p&lt;0.05), indicating improved reperfusion of organ tissues. While AST has shown a significant drop in the BTT-survival group (67.10 vs. 56.17, p&lt;0.05), indicating improved liver function. During the support, 3 patients with peripheral cannulation and 2 patients with mini-incision were able to ambulate early. The types of complication seen were similar to those reported with CentriMag, but the rates of bleeding (15%) and hemolysis (0%) were much lower. In conclusion, MoyoAssist® Extra-VAD has demonstrated its safety and efficacy for short-to-mid-term support of patients with acute heart failure and cardiogenic shock.

Review of Intraoral Vasculature and Implications on Incision Designs of Periodontal and Implant Surgeries.

Currently, the incision design for periodontal and implant surgeries is mainly based on the surgeon's personal preference. The primary aim of this study is to review the intricate periodontal microvascular system and to illustrate the potential impact of commonly applied flap designs on the integrity of this system. A complete literature electronic search resulted in 37 relevant articles. The maxillary, facial, and lingual arteries supply the microvasculature system, including the supraperiosteal, intraligamental, and intraosseous arterioles. These arterioles have their own territories yet are extensively interconnected. The impact of common papilla management techniques are discussed, including tunneling; papilla base, incision, and preservation; and flap-releasing incisions. Flap design can impact reperfusion and blood inflow in the early healing phase, which eventually influences wound closure probability, healing speed, surgical predictability, tissue volume change, and postoperative morbidity. Future studies on the three-dimensional distribution of microvasculature and clinical impact of various flap designs on tissue reperfusion can lead to evidence-based incision selection and improved wound-healing outcomes.