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Background: Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed. Aims: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services. Methods: We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary. Results: Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and PRE-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (63% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulance services (80% in HICs) around the world. Conclusion: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available patient-level data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world. [ABSTRACT FROM AUTHOR]

Background and Purpose: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients. Methods: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short‐term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long‐term outcome was 90‐day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p‐value ≤.05. Results: Among 73 patients, median age was 66 (interquartile range 54‐76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes. Conclusions: Our multisite analysis shows that favorable short‐term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger‐scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients. [ABSTRACT FROM AUTHOR]

Introduction: Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote ischemic per- conditioning (RIPerC) exerts cardioprotective effects via the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS)/apelin pathway. Methods: Renal ischemia-reperfusion injury (I/R) was induced by bilateral occlusion of the renal pedicles for 60 minutes, followed by 24 hours of reperfusion; sham-operated rats served as controls. RIPerC was induced by four cycles (5 minutes) of limb ischemia-reperfusion along with bilateral renal ischemia. The functional disturbance was evaluated by renal (BUN and creatinine) and cardiac (troponin I and lactate dehydrogenase) injury biomarkers. Results: Renal I/R injury increased renal and cardiac injury biomarkers that were reduced in the RIPerC group. Histopathological findings of the kidney and heart were also suggestive of amelioration injury-induced changes in the RIPerC group. Assessment of cardiac electrophysiology revealed that RIPerC ameliorated the decline in P wave duration without significantly affecting other cardiac electrophysiological changes. Further, renal I/R injury increased the plasma (322.40±34.01 IU/L), renal (8.27±1.10 mIU/mg of Protein), and cardiac (68.28±10.28 mIU/mg of protein) angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite (25.47±2.01 & 16.62±3.05 μmol/L) and nitrate (15.47±1.33 & 5.01±0.96 μmol/L) levels; these changes were reversed by RIPerC. Further, renal ischemia-reperfusion injury significantly (P =0.047) decreased the renal (but not cardiac) apelin mRNA expression, while renal and cardiac ACE2 (P <0.05)>P=0.043) mRNA expressions were significantly increased compared to the sham group; these effects were largely reversed by RIPerC. Conclusion: Our results indicated that RIPerC protects the heart against renal ischemia- reperfusion injury, likely via interaction of the apelin with the RAS/iNOS pathway. [ABSTRACT FROM AUTHOR]

The objective of this study is to comprehensively examine the available data on the efficacy and safety of intensive blood pressure lowering (IBPL) compared to standard blood pressure control (SBPC) in patients with acute ischemic stroke following reperfusion therapy. A comprehensive search was conducted using 4 databases, including PubMed, Cochrane, Embase, and Web of Science to collect relevant articles from inception to December 2023. The endpoints were the condition of the patient measured by the modified Rankin scale (mRS, range value from 0 [no symptoms] to 6 [death]) at 90 days, symptomatic intracranial hemorrhage, death within 90 days, recurrent ischemic stroke, and intracranial hemorrhage (ICH). Seven eligible studies involving 4499 participants (2218 patients in IBPL group and 2281 patients in SBPC group) were included in the analysis. Both groups demonstrated similar baseline characteristics. Within the endovascular therapy (EVT) subgroup, the IBPL group exhibited worse mRS than in SBPC group. After EVT, different IBPL targets showed worse outcomes in the mRS for the SBP <140 mmHg and SBP <120 mmHg subgroups, with no difference between IBPL and SBPC groups in the SBP <130 mmHg subgroup. In the intravenous thrombolysis subgroup, although the IBPL group exhibited less ICH, the long-term functional outcomes were not improved significantly. The IBPL group exhibited a less favorable functional outcome after EVT. Moreover, no worse functional outcomes were noticed in the SBP <130 mmHg subgroup after EVT. However, the functional outcome was similar after intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) and its associated complications including ventricular arrhythmias and heart failure are responsible for a significant incidence of morbidity and mortality worldwide. The ensuing cardiomyocyte loss results in neurohormone‐driven cardiac remodeling, which leads to chronic heart failure in MI survivors. Ivabradine is a heart rate modulation agent currently used in treatment of chronic heart failure with reduced ejection fraction. The canonical target of ivabradine is the hyperpolarization‐activated cyclic nucleotide‐gated channels (HCN) in cardiac pacemaker cells. However, in post‐MI hearts, HCN can also be expressed ectopically in non‐pacemaker cardiomyocytes. There is an accumulation of intriguing evidence to suggest that ivabradine also possesses cardioprotective effects that are independent of heart rate reduction. This review aims to summarize and discuss the reported cardioprotective mechanisms of ivabradine beyond heart rate modulation in myocardial infarction through various molecular mechanisms including the prevention of reactive oxygen species‐induced mitochondrial damage, improvement of autophagy system, modulation of intracellular calcium cycling, modification of ventricular electrophysiology, and regulation of matrix metalloproteinases. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to investigate the impact of time interval between start of intravenous thrombolysis (IVT) to start of endovascular thrombectomy (EVT) on stroke outcomes. Methods: Data from the Quality Improvement and Clinical Research (QuICR) provincial stroke registry from Alberta, Canada, were used to identify stroke patients who received IVT and EVT from January 2015 to December 2019. We assessed the impact of the time interval between IVT bolus to EVT puncture (needle-to-puncture times [NPT]) on outcomes. Radiological outcomes included successful initial recanalization (revised Arterial Occlusive Lesion 2b–3), successful initial and final reperfusion (modified thrombolysis in cerebral infarction 2b–3). Clinical outcomes were 90-day modified Rankin Scale (mRS) and mortality. Results: Of the 680 patients, 233 patients (median age: 73, 41% females) received IVT + EVT. Median NPT was 38 min (IQR, 24–60). Arrival during working hours was independently associated with shorter NPT (p < 0.001). Successful initial recanalization and initial and final reperfusion were observed in 12%, 10%, and 83% of patients, respectively. NPT was not associated with initial successful recanalization (OR 0.97 for every 10-min increase of NPT, 95% CI: 0.91–1.04), initial successful reperfusion (OR 1.01, 95% CI: 0.96–1.07), or final successful reperfusion (OR: 1.03, 95% CI: 0.97–1.08). Every 10-min delay in NPT was associated with lower odds of functional independence at 90 days (mRS ≤2; OR: 0.93; 95% CI, 0.88–0.97). Patients with shorter NPT (≤38 min) had lower 90-day mRS scores (median 1 vs. 3; OR: 0.54 [0.31–0.91]) and had lower mortality (6.1% vs. 21.2%; OR, 0.23 [0.10–0.57]) than the longer NPT group. Conclusion: Shorter NPT did not impact reperfusion outcomes but was associated with better clinical outcome. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) ranks among the top contributors to sudden death and disability worldwide. It should be noted that current therapies always cause increased reperfusion damage. Evidence suggests that humanin (HN) reduces mitochondrial dysfunction to have cardio-protective effects against MI-reperfusion injury. In this context, we hypothesized that HN may attenuate MI-reperfusion injury by alleviating lymphatic endothelial cells dysfunction through the regulation of mitophagy. In this study, primary lymphatic endothelial cells were selected as the experimental model. Cells were maintained under 1% O2 to induce a hypoxic phenotype. For in vivo experiments, the left coronary arteries of C57/BL6 mice were clamped for 45 min followed by 24 h reperfusion to develop MI-reperfusion injury. The volume of infarcted myocardium in MI-reperfusion injury mouse models were TTC staining. PCR and western blot were used to quantify the expression of autophagy-, mitophagy- and mitochondria-related markers. The fibrosis and apoptosis in the ischemic area were evaluated for Masson staining and TUNEL respectively. We also used western blot to analyze the expression of VE-Cadherin in lymphatic endothelial cells. We firstly exhibited a specific mechanism by which HN mitigates MI-reperfusion injury. We demonstrated that HN effectively reduces such injury in vivo and also inhibits dysfunction in lymphatic endothelial cells in vitro. Importantly, this inhibitory effect is mediated through BNIP3-associated mitophagy. In conclusion, HN alleviates myocardial infarction-reperfusion injury by inhibiting lymphatic endothelial cells dysfunction, primarily through BNIP3-mediated mitophagy. [ABSTRACT FROM AUTHOR]

The mechanisms of cerebral ischemia–reperfusion injury (IRI) limitation by remote ischemic postconditioning (RPC) are of interest because the latter may positively influence functional recovery after cerebral ischemia. The study was aimed to assess the role of plasma proteins syndecan-1 (SDC-1) and annexin-5 (ANXA-5) in limiting cerebral IRI by RPC in a middle cerebral artery occlusion (MCAO) model in male Wistar rats. The animals were randomized into three groups: (1) control sham-operated rats (SO group), (2) rats with 30-min MCAO-induced ischemia (MCAO group), (3) rats with 30-min MCAO-induced ischemia followed by RPC (MCAO + RPC group). SDC-1 plasma levels, as assessed by ELISA, in MCAO (41.4 ± 1.3 ng/mL) and MCAO + RPC (67.8 ± 5.8 ng/mL) rats were, respectively, by 30% (p < 0.05) and 112% (p < 0.01) higher than in SO control (31.9 ± 1.1 ng/mL). No intergroup differences in ANXA-5 plasma levels were detected. Cerebral infarct volume in MCAO and MCAO + RPC rats accounted for 32.0 ± 2.5 and 13.6 ± 1.3% of the total brain volume, respectively (p < 0.05). Cerebral edema volume in MCAO and MCAO + RPC rats were 47.0 ± 3.3 and 16.0 ± 2.1%, respectively (p < 0.05). In MCAO + RPC animals, correlation analysis revealed a high direct correlation between infarct size and right forelimb muscular strength (grip strength test, 3.9 ± 0.8 H, p > 0.5; KK = 0.72, p < 0.05) and a very high inverse correlation between infarct size and right hindlimb capillary blood flow (Doppler flowmetry, r = –0.98, p < 0.01). Animals' neurologic deficits were assessed by the Garcia scoring scale, while their locomotor coordination was assessed in the Rotarod test. It is assumed that SDC-1 plasma protein may serve as a potential regulator of the infarct size-limiting effect of remote ischemic postconditioning, which is determinative for functional recovery. [ABSTRACT FROM AUTHOR]

Objective: The treatment paradigm for acute ischemic stroke has undergone several major changes in the past decade, contributing to improved patient prognosis in clinical practice. However, the extent to which these changes have affected patient prognosis in the real-world is yet to be clarified. This study aimed to evaluate the real-world impact of modern reperfusion therapy for acute ischemic stroke using data from the National Health Insurance Service in Korea. Methods: This study included patients aged 18-80 years who were admitted via the emergency room with an I63 code between 2011 and 2020. The rates of intravenous thrombolysis use and endovascular treatment according to the year of admission were investigated. Furthermore, the rates of decompressive craniectomy and 3-month mortality were also analyzed. The 10-year observational period was divided into three periods based on the 2015 guideline change as follows: prior, 2011-2014; transitional, 2015-2016; and modern, 2017-2020. Results: A total of 307117 patients (mean age, 65.7±10.9 years) were included, and most patients were male (59.7%). The rate of endovascular treatment gradually increased during the study period from 0.71% in the prior period to 1.32% in the transitional period and finally to 1.85% in the modern period. Meanwhile, the 3-month mortality rate gradually decreased from 4.78% in the prior period to 4.03% in the transitional period and to 3.71% in the modern period. Conclusion: In Korea, the mortality rate decreased as the rate of modern reperfusion therapy increased in patients with acute ischemic stroke. Overall, technical and scientific advances in reperfusion therapy have improved the outcome of patients with acute ischemic stroke in Korea. [ABSTRACT FROM AUTHOR]

(1) Background: Years of research have identified ischemic preconditioning (IPC) as a crucial endogenous protective mechanism against myocardial ischemia–reperfusion injury, enhancing the myocardial cell's tolerance to subsequent ischemic damage. High-intensity interval training (HIIT) is promoted by athletes because it reduces exercise duration and improves metabolic response and cardiopulmonary function. Our objective was to evaluate and compare whether HIIT and IPC could reduce myocardial ischemia and reperfusion injury in rats. (2) Methods: Male Sprague-Dawley rats were divided into four groups: sham surgery, coronary artery occlusion (CAO), high-intensity interval training (HIIT), and ischemic preconditioning (IPC). The CAO, HIIT, and IPC groups experienced 40 min of coronary artery occlusion followed by 3 h of reperfusion to induce myocardial ischemia–reperfusion injury. Subsequently, the rats were sacrificed, and blood samples along with cardiac tissues were examined. The HIIT group received 4 weeks of training before surgery, and the IPC group underwent preconditioning before the ischemia–reperfusion procedure. (3) Results: The HIIT and IPC interventions significantly reduced the extent of the myocardial infarction size and the levels of serum troponin I and lactate dehydrogenase. Through these two interventions, serum pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were significantly decreased, while the anti-inflammatory cytokine IL-10 was increased. Furthermore, the expression of pro-apoptotic proteins PTEN, caspase-3, TNF-α, and Bax in the myocardium was reduced, and the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) was increased, ultimately reducing cellular apoptosis in the myocardium. In conclusion, both HIIT and IPC demonstrated effective strategies with potential for mitigating myocardial ischemia–reperfusion injury for the heart. [ABSTRACT FROM AUTHOR]

Objective(s): We aimed to investigate the levels of transient receptor potential melastatin (TRPM) gene expression, and the antioxidant and histopathologic effect of thymoquinone (Tmq) in the hepatic I/R rat model. Materials and Methods: Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Sham; Group 3: Hepatic I/R (45 min/45 min); Group 4: Tmq (50 mg/kg); Group 5: Tmq+I/R (ten days before I/R at the dose of 50 mg/kg of Tmq). The hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular clamp in the ischemia groups. The liver tissues and blood samples that were taken at the end of the study were evaluated for histopathologic and biochemical analysis. Besides TRPM gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL, and apoptosis parameters statistically decreased in Tmq and Tmq+I/R groups in comparison with the I/R group in histopathological evaluation. Results: It was observed that biochemical parameters, AST, ALT, GGT, LDH, creatinine, and urea levels significantly increased in the I/R group as compared with, sham, Tmq, and Tmq+I/R groups. It was found that TRPM2,6,7,8 gene expression decreased significantly in Tmq+I/R groups as compared to the I/R group. Conclusion: We showed that thymoquinone can inhibit the entry of Ca+2 into the cell by decreasing TRPM2,6,7,8 gene expression. Based on our findings, we think that Tmq application in the treatment of liver diseases due to I/R damage may be important in terms of both ischemia and apoptosis and can also be used in the treatment of liver-related diseases. [ABSTRACT FROM AUTHOR]

Objective(s): Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy. Materials and Methods: The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase a2 (AMPKa2) KO mice were used to investigate the underlying mechanism. Results: In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKa2. Conclusion: The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies. [ABSTRACT FROM AUTHOR]

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel's sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia. [ABSTRACT FROM AUTHOR]

Endothelial pro-inflammatory activation is pivotal in cardiac ischemia–reperfusion (I/R) injury pathophysiology. The dried flower bud of Edgeworthia gardneri (Wall.) Meisn. (EG) is a commonly utilized traditional Tibetan medicine. However, its role in regulating endothelium activation and cardiac I/R injury has not been investigated. Herein, we showed that the administration of EG ethanolic extract exhibited a potent therapeutic efficacy in ameliorating cardiac endothelial inflammation (p < 0.05) and thereby protecting against myocardial I/R injury in rats (p < 0.001). In line with the in vivo findings, the EG extract suppressed endothelial pro-inflammatory activation in vitro by downregulating the expression of pro-inflammatory mediators (p < 0.05) and diminishing monocytes' firm adhesion to endothelial cells (ECs) (p < 0.01). Mechanistically, we showed that EG extract inhibited the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways to attenuate EC-mediated inflammation (p < 0.05). Collectively, for the first time, this study demonstrated the therapeutic potential of EG ethanolic extract in alleviating I/R-induced inflammation and the resulting cardiac injury through its inhibitory role in regulating endothelium activation. [ABSTRACT FROM AUTHOR]

Background and purpose: In patients with acute ischemic stroke, hyponatremia (plasma sodium < 136 mmol/L) is common and associated with unfavorable outcomes. However, data are limited for patients who underwent intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Therefore, our aim was to assess the impact of hyponatremia on postreperfusion outcomes. Methods: We analyzed data of consecutive patients who presented with acute ischemic stroke and were treated with IVT and/or EVT at Isala Hospital, the Netherlands, in 2019 and 2020. The primary outcome measure was the adjusted common odds ratio (acOR) for a worse modified Rankin Scale (mRS) score at 3‐month follow‐up. Secondary outcomes included symptomatic intracranial hemorrhage, in‐hospital mortality, infarct core, and penumbra volumes. Results: Of the 680 patients (median age = 73 years, 49% female, median National Institutes of Health Stroke Scale = 5), 430 patients (63%) were treated with IVT, 120 patients (18%) with EVT, and 130 patients (19%) with both. Ninety‐two patients (14%) were hyponatremic on admission. Hyponatremia was associated with a worse mRS score at 3 months (acOR = 1.76, 95% confidence interval [CI] = 1.12–2.76) and in‐hospital mortality (aOR = 2.39, 95% CI = 1.23–4.67), but not with symptomatic intracranial hemorrhage (OR = 1.17, 95% CI = 0.39–3.47). Hyponatremia was also associated with a larger core (17.2 mL, 95% CI = 2.9–31.5) and core to penumbra ratio (55.0%, 95% CI = 7.1–102.9). Conclusions: Admission hyponatremia in patients with acute ischemic stroke treated with IVT and/or EVT was independently associated with unfavorable postreperfusion outcomes, a larger infarct core, and a larger core to penumbra ratio. Future studies should address whether correction of hyponatremia improves the prognosis. [ABSTRACT FROM AUTHOR]

Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged. Moreover, we revealed ischaemic pericytes to be fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 h post stroke. Despite sustaining acute membrane damage, we observed that over half of all cortical pericytes survived ischaemia and responded to vasoactive stimuli, upregulated unique transcriptomic profiles and replicated. Finally, we demonstrated the delayed recovery of capillary diameter by ischaemic pericytes after reperfusion predicted vessel reconstriction in the subacute phase of stroke. Cumulatively, these findings demonstrate that surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischaemic stroke. [ABSTRACT FROM AUTHOR]

Introduction: Medium vessel occlusion (MeVO) accounts for 30% of acute ischemic stroke cases. The risk/benefit profile of endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or the combination of the two (bridging therapy (BT)) is still unclear in MeVO. Here, we compare reperfusion strategies in MeVO for clinical and radiological outcomes. Methods: This prospective single center study enrolled consecutive patients with AIS due to primary MeVO undergoing IVT, EVT, or BT at a comprehensive stroke center. Primary outcome was good functional status, defined as modified Rankin Scale (mRS) 0–2 at 3-month follow-up. Additional outcomes included mortality, successful recanalization, defined as mTICI ≥ 2b, stroke severity at discharge, and symptomatic intracerebral hemorrhage (sICH) according to SITS-MOST criteria. Logistic regression was modeled to define independent predictors of the primary outcome. Results: Overall, 180 consecutive people were enrolled (IVT = 59, EVT = 38, BT = 83), mean age 75. BT emerged as independent predictor of primary outcome (OR = 2.76, 95% CI = 1.08–7.07) together with age (OR = 0.94, 95% CI = 0.9–0.97) and baseline NIHSS (OR = 0.88, 95% CI = 0.81–0.95). BT associated with a 20% relative increase in successful recanalization compared to EVT (74.4 vs 56.4%, p = 0.049). Rates of sICH (1.1%) and procedural complications (vasospasm 4.1%, SAH in 1.7%) were very low, with no difference across groups. Discussion: BT may carry a higher chance of good functional outcome compared to EVT/IVT only in people with AIS due to MeVO, with marginally higher rates of successful recanalization. Randomized trials are needed to define optimal treatment tailoring for MeVO. [ABSTRACT FROM AUTHOR]

Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia–reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR. [ABSTRACT FROM AUTHOR]

Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries, thereby increasing penumbra reperfusion. After reperfusion therapy, 46% of patients are able to live independently 3 months after stroke onset. MicroRNAs (miRNAs) are essential regulators in the development of cerebral ischemia/reperfusion injury and the efficacy of the applied treatment. The first aim of this study was to examine the change in serum miRNA levels via next-generation sequencing (NGS) 10 days after the onset of acute stroke and reperfusion treatment. Next, the predictive values of the bioinformatics analysis of miRNA gene targets for the assessment of brain ischemic response to reperfusion treatment were explored. Human serum samples were collected from patients on days 1 and 10 after stroke onset and reperfusion treatment. The samples were subjected to NGS and then validated using qRT-PCR. Differentially expressed miRNAs (DEmiRNAs) were used for enrichment analysis. Hsa-miR-9-3p and hsa-miR-9-5p expression were downregulated on day 10 compared to reperfusion treatment on day 1 after stroke. The functional analysis of miRNA target genes revealed a strong association between the identified miRNA and stroke-related biological processes related to neuroregeneration signaling pathways. Hsa-miR-9-3p and hsa-miR-9-5p are potential candidates for the further exploration of reperfusion treatment efficacy in stroke patients. [ABSTRACT FROM AUTHOR]

Ischemia‐reperfusion injury is an event concerning any organ under a procedure of transplantation. The early result of ischemia is hypoxia, which causes malfunction of mitochondria and decrease in cellular ATP. This leads to disruption of cellular metabolism. Reperfusion also results in cell damage due to reoxygenation and increased production of reactive oxygen species, and later by induced inflammation. In damaged and hypoxic cells, the endoplasmic reticulum (ER) stress pathway is activated by increased amount of damaged or misfolded proteins, accumulation of free fatty acids and other lipids due to inability of their oxidation (lipotoxicity). ER stress is an adaptive response and a survival pathway, however, its prolonged activity eventually lead to induction of apoptosis. Sustaining cell functionality in stress conditions is a great challenge for transplant surgeons as it is crucial for maintaining a desired level of graft vitality. Pathways counteracting negative consequences of ischemia‐reperfusion are autophagy and lipid droplets (LD) metabolism. Autophagy remove damaged organelles and molecules driving them to lysosomes, digested simpler compounds are energy source for the cell. Mitophagy and ER‐phagy results in improvement of cell energetic balance and alleviation of ER stress. This is important in sustaining metabolic homeostasis and thus cell survival. LD metabolism is connected with autophagy as LD are degraded by lipophagy, a source of free fatty acids and glycerol—thus autophagy and LD can readily remove lipotoxic compounds in the cell. In conclusion, monitoring and pharmaceutic regulation of those pathways during transplantation procedure might result in increased/improved vitality of transplanted organ. [ABSTRACT FROM AUTHOR]

The STEMI-DTU pilot study tested the early safety and practical feasibility of left ventricular (LV) unloading with a trans-valvular pump before reperfusion. In the intent-to-treat cohort, no difference was observed for microvascular obstruction (MVO) or infarct size (IS) normalized to either the area at risk (AAR) at 3–5 days or total LV mass (TLVM) at 3–5 days We now report a per protocol analysis of the STEMI-DTU pilot study. In STEMI-DTU STUDY 50 adult patients (25 in each arm) with anterior STEMI [sum of precordial ST-segment elevation (ΣSTE) ≥4 mm] requiring primary percutaneous coronary intervention (PCI) were enrolled. Only patients who met all inclusion and exclusion criteria were included in this analysis. Cardiac magnetic resonance (CMR) imaging 3–5 days after PCI quantified IS/AAR and IS/TLVM and MVO. Group differences were assessed using Student's t -tests and linear regression (SAS Version-9.4). Of the 50 patients enrolled, 2 died before CMR imaging. Of the remaining 48 patients those without CMR at 3–5 days (n = 8), without PCI of a culprit left anterior descending artery lesion (n = 2), with OHCA (n = 1) and with ΣSTE < 4 mm (n = 5) were removed from this analysis leaving 32/50 (64 %) patients meeting all inclusion and exclusion criteria (U-IR, n = 15; U-DR, n = 17) as per protocol. Despite longer symptom-to-balloon times in the U-DR arm (228 ± 80 vs 174 ± 59 min, p < 0.01), IS/AAR was significantly lower with 30 min of delay to reperfusion in the presence of active LV unloading (47 ± 16 % vs 60 ± 15 %, p = 0.02) and remained lower irrespective of the magnitude of precordial ΣSTE. MVO was not significantly different between groups (1.5 ± 2.8 % vs 3.5 ± 4.8 %, p = 0.15). Among patients who received LV unloading within 180 min of symptom onset, IS/AAR was significantly lower in the U-DR group. In this per-protocol analysis of the STEMI-DTU pilot study we observed that LV unloading for 30 min before reperfusion significantly reduced IS/AAR compared to LV unloading and immediate reperfusion, whereas in the ITT cohort no difference was observed between groups. This observation supports the design of the STEMI-DTU pivotal trial and suggests that strict adherence to the study protocol can significantly influence the outcome. • LV unloading plus delayed reperfusion may reduce infarct size. • LV unloading plus delayed reperfusion may reduce microvascular obstruction. • This per protocol analysis supports the design of the ongoing STEMI-DTU pivotal trial. [ABSTRACT FROM AUTHOR]

Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia. [ABSTRACT FROM AUTHOR]

Aims: With the progress of thrombectomy technology, the vascular recanalization rate of patients with stroke has been continuously improved, but the proportion of futile recanalization (FR) is still quite a few. The long‐term prognosis and survival of patients with FR and its influencing factors remain unclear. Methods: Consecutive patients who received endovascular treatment (EVT) for ischemic stroke were enrolled between 2013 and 2021 from a single‐center prospectively registry study. We evaluated the long‐term outcome of these patients by Kaplan–Meier survival analysis, and the multivariable logistic regression curve was performed to analyze influencing factors. Results: Among 458 patients with FR, 56.4% of patients survived at 1 year, and 50.4% at 2 years. In the multivariate regression analysis, age, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), posterior circulation infarct, general anesthesia, symptomatic intracerebral hemorrhage (sICH), and decompressive craniectomy were found to be related to unfavorable outcomes in long‐term. Age, premorbid mRS, NIHSS, general anesthesia, and sICH were predictors of long‐term mortality. Conclusions: Futile recanalization accounts for a large proportion of stroke patients after thrombectomy. This study on the long‐term prognosis of such patients is beneficial to the formulation of treatment plans and the prediction of therapeutic effects. [ABSTRACT FROM AUTHOR]

Tomographic perfusion imaging techniques are integral to translational stroke research paradigms that advance our understanding of the disease. Functional ultrasound (fUS) is an emerging technique that informs on cerebral blood volume (CBV) through ultrasensitive Doppler and flow velocity (CBFv) through ultrafast localization microscopy. It is not known how experimental results compare with a classical CBV-probing technique such as dynamic susceptibility contrast-enhanced perfusion MRI (DSC-MRI). To that end, we assessed hemodynamics based on uUS (n = 6) or DSC-MRI (n = 7) before, during and up to three hours after 90-minute filament-induced middle cerebral artery occlusion (MCAO) in rats. Recanalization was followed by a brief hyperperfusion response, after which CBV and CBFv temporarily normalized but progressively declined after one hour in the lesion territory. DSC-MRI data corroborated the incomplete restoration of CBV after recanalization, which may have been caused by the free-breathing anesthetic regimen. During occlusion, MCAO-induced hypoperfusion was more discrepant between either technique, likely attributable to artefactual signal mechanisms related to slow flow, and processing algorithms employed for either technique. In vivo uUS- and DSC-MRI-derived measures of CBV enable serial whole-brain assessment of post-stroke hemodynamics, but readouts from both techniques need to be interpreted cautiously in situations of very low blood flow. [ABSTRACT FROM AUTHOR]

Intestinal ischemia-reperfusion injury (IRI) is a potentially severe clinical syndrome after major surgical procedures. In addition to causing intestinal mucosa injury, intestinal IRI further damages distant organs, causing the severity of the condition in patients. So far, effective therapy for intestinal IRI is still absent, and the survival rate of the patients is low. Previous experimental studies have shown that some anesthetics can alleviate intestinal IRI and protect organs while exerting their pharmacological effects, indicating that reasonable perioperative anesthesia management may provide potential benefits for patients to avoid intestinal IRI. These meaningful findings drive scholars to investigate the mechanism of anesthetics in treating intestinal IRI in-depth to discuss the possible new clinical uses. In the present mini-review, we will introduce the protective effects of different anesthetics in intestinal IRI to help us enrich our knowledge in this area. [ABSTRACT FROM AUTHOR]

Background. The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Methods. Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. Results. It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. Conclusion. EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

Intestinal motility is governed in part by bioelectrical slow-waves and spike-bursts. Mesenteric ischemia is a substantial clinical challenge, but its electrophysiological and contractile mechanisms are not well understood. Simultaneous high-resolution bioelectrical and video mapping techniques were used to capture the changes in slow-waves, spike-bursts, and contractile activity during baseline, ischemia, and reperfusion periods. Experiments were performed on anesthetized pigs where intestinal contractions were quantified using surface strain and diameter measurements, while slow-wave and spike-bursts were quantified using frequency and amplitude. Slow-waves entrainment within the ischemic region diminished during ischemia, resulting in irregular slow-wave activity and a reduction in the frequency from 12.4 ± 3.0 cycles-per-minute (cpm) to 2.5 ± 2.7 cpm (p = 0.0006). At the end of the reperfusion period, normal slow-wave entrainment was observed at a frequency of 11.5 ± 2.9 cpm. There was an increase in spike-burst activity between the baseline and ischemia periods (1.1 ± 1.4 cpm to 8.7 ± 3.3 cpm, p = 0.0003) along with a spasm of circumferential contractions. At the end of the reperfusion period, the frequency of spike-bursts decreased to 2.7 ± 1.4 cpm, and contractions subsided. The intestine underwent tonal contraction during ischemia, with the diameter decreasing from 29.3 ± 2.6 mm to 21.2 ± 6.2 mm (p = 0.0020). At the end of the reperfusion period, the intestinal diameter increased to 27.3 ± 3.9 mm. The decrease in slow-wave activity, increase in spike-bursts, and tonal contractions can objectively identify ischemic segments in the intestine. It is anticipated that the use of electrophysiological slow-wave and spike-burst biomarkers, along with contractile measures, could identify mesenteric ischemia in surgical settings and allow an objective biomarker for successful revascularization. [ABSTRACT FROM AUTHOR]

The utilization of COVID-19-positive donors has expanded the donor pool for transplantation since the initiation of COVID allograft utilization protocols. However, the biopsy-proven PCR transmission rate of COVID-19 from these allografts has not been well documented. In August 2021, an institutional COVID-19-positive allograft protocol was implemented for liver and kidney transplants. Post-reperfusion liver biopsies were obtained intra-operatively to evaluate for COVID-19 RNA, and post-operative day 7 nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) swabs were collected. The primary endpoints evaluated included COVID-19 RNA on biopsy and COVID-19 detected via nasopharyngeal RT-PCR swab on post-operative day 7. A total of 20 vaccinated recipients underwent transplantation (17 liver only, 3 simultaneous liver and kidney) with whole liver allografts from 20 COVID-19-positive deceased donors between August 2021 and April 2022. 95% (19/20) of donors were asymptomatic at the time of donation. On post-reperfusion liver allograft biopsies, COVID-19 RNA was found in 10% (2/20) of the samples. All the recipients were COVID-19-negative on post-operative day 7 nasopharyngeal RT-PCR, showing a 0% transmission rate of COVID-19 from the positive allografts. The use of COVID-19 allografts appears to be a safe practice, with no PCR-detectable transmission of COVID-19 despite 10% of the liver allografts having COVID-19 RNA present on post-reperfusion biopsy. [ABSTRACT FROM AUTHOR]

Background: Demethylnobiletin (DN), with a variety of biological activities, is a polymethoxy‐flavanone (PMF) found in citrus. In the present study, we explored the biological activities and potential mechanism of DN to improve cerebral ischemia reperfusion injury (CIRI) in rats, and identified DN as a novel neuroprotective agent for patients with ischemic brain injury. Methods: Rat CIRI models were established via middle cerebral artery occlusion (MCAO). Primary nerve cells were isolated and cultured in fetal rat cerebral cortex in vitro, and oxygen–glucose deprivation/reperfusion (OGD/R) models of primary nerve cells were induced. After intervention with DN with different concentrations in MCAO rats and OGD/R nerve cells, 2,3,5‐triphenyltetrazolium chloride staining was used to quantify cerebral infarction size in CIRI rats. Modified neurological severity score was utilized to assess neurological performance. Histopathologic staining and live/dead cell‐viability staining was used to observe apoptosis. Levels of glutathione (GSH), superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in tissues and cells were detected using commercial kits. DN level in serum and cerebrospinal fluid of MCAO rats were measured by liquid chromatography tandem mass spectrometry. In addition, expression levels of proteins like Kelch like ECH associated protein 1 (Keap1), nuclear factor erythroid 2‐related factor 2 (Nfr2) and heme oxygenase 1 (HO‐1) in the Nrf2/HO‐1 pathway, and apoptosis‐related proteins like Cleaved caspase‐3, BCL‐2‐associated X protein (Bax) and B‐cell lymphoma‐2 (Bcl‐2) were determined by Western blot and immunofluorescence. Results: DN can significantly enhance neurological function recovery by reducing cerebral infarction size and weakening neurocytes apoptosis in MCAO rats. It was further found that DN could improve oxidative stress (OS) injury of nerve cells by bringing down MDA and ROS levels and increasing SOD and GSH levels. Notably, DN exerts its pharmacological influences through entering blood–brain barrier. Mechanically, DN can reduce Keap1 expression while activate Nrf2 and HO‐1 expression in neurocytes. Conclusions: The protective effect of DN on neurocytes have been demonstrated in both in vitro and in vivo circumstances. It deserves to be developed as a potential neuroprotective agent through regulating the Nrf2/HO‐1 signaling pathway to ameliorate neurocytes impairment caused by OS. [ABSTRACT FROM AUTHOR]

Cerebral ischemia and reperfusion are related to various situations like injuries after various traumas, oxidative stress, increased calcium ion, capillary hypoperfusion, microvascular hyperpermeability, leukocyte infiltration, and blood–brain barrier disruption. An antidepressant Agomelatine which is a melatonin receptor (MT1/MT2) agonist and serotonin receptor (5‐HT2C) antagonist has been reported by studies to have antioxidant and anti‐inflammatory effects. In our study, we aimed to detect the effects of citrate‐coated silver nanoparticle‐loaded agomelatine application on neurodegeneration, endoplasmic reticulum stress, autophagic and apoptotic cell death, inflammation, and P2X7R expression in the cerebral ischemia–reperfusion model to facilitate the passage of blood–brain barrier. Forty two Sprague–Dawley rats in total were divided into six equal groups (n:7) and applications were performed. Acute cerebral injury in the ischemia–reperfusion model was created 2 h after internal carotid artery ligation in rats and then at the 2nd hour of reperfusion citrate‐coated silver nanoparticles loaded with Agomelatine were applied. Twenty four hours later, neurologic analysis on animals in experimental groups was performed, animals were decapitated and GSH, GPx, SOD, CAT, MDA, IL‐1β, and TNF‐α parameters were examined after taking blood and the cerebral tissue samples. As a result, it was determined that ischemia–reperfusion caused endoplasmic reticulum stress in the cerebral tissues and thus caused cellular injury. [ABSTRACT FROM AUTHOR]

Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia–reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm2 for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood–brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia–reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI. [ABSTRACT FROM AUTHOR]

Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41-50% of patients with ST-segment elevation myocardial infarction and PCI. The occurrence of IMH is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO. The appearance of MVO is associated with infarct size, the duration of ischemia of the heart, and myocardial edema. However, there is no conclusive evidence that myocardial edema plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell damage in MVO formation remains unclear in patients with AMI and PCI. It is unclear whether nitric oxide production is reduced in patients with MVO. Only indirect evidence on the involvement of inflammation in the development of MVO has been obtained. The role of reactive oxygen species (ROS) in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied. The significance of the balance of thromboxane A2, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is currently unknown. Conclusive evidence regarding the role of coronary artery spasm in the development of MVhasn’t been established. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI has not previously been performed. It is unclear whether epinephrine aggravates reperfusion necrosis of cardiomyocytes. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca2+ channel blockers result in the long-term improvement of coronary blood flow in patients with MVO. [ABSTRACT FROM AUTHOR]

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia–reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase–MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS. [ABSTRACT FROM AUTHOR]

Hyperchloremia and hypernatremia are associated with higher mortality in ischemic stroke, but it remains unclear whether their influence directly contributes to ischemic injury. We investigated the impact of 0.9% sodium chloride (154 mM NaCl), 0.9% sodium acetate (167 mM CH3COONa), and their different combinations (3:1, 2:1, and 1:1) on microglial (HMC-3) and neuronal (differentiated SH-SY5Y) survival during oxygen–glucose deprivation/reperfusion (OGD/R). Further, we assessed the effect of hyperchloremia and hypernatremia-treated and OGD/R-induced HMC-3-conditioned media on differentiated SH-SY5Y cells under OGD/R conditions. We performed cell viability, cell toxicity, and nitric oxide (NO) release assays and studied the alteration in expression of caspase-1 and caspase-3 in different cell lines when exposed to hyperchloremia and hypernatremia. Cell survival was decreased in 0.9% NaCl, 0.9% CH3COONa, combinations of HMC-3 and differentiated SH-SY5Y, and differentiated SH-SY5Y cells challenged with HMC-3-conditioned media under normal and OGD/R conditions. Under OGD/R conditions, differentiated SH-SY5Y cells were less likely to survive exposure to 0.9% NaCl. Expression of caspase-1 and caspase-3 in HMC-3 and differentiated SH-SY5Y cells was altered when exposed to 0.9% NaCl, 0.9% CH3COONa, and their combinations. A total of 0.9% NaCl and 0.9% CH3COONa and their combinations decreased the NO production in HMC-3 cells under normal and OGD/R conditions. Both hypernatremia and hyperchloremia reduced the survival of HMC-3 and differentiated SH-SY5Y cells under OGD/R conditions. Based on the OGD/R in vitro model that mimics human ischemic stroke conditions, it possibly provides a link for the increased death associated with hyperchloremia or hypernatremia in stroke patients. [ABSTRACT FROM AUTHOR]

Aims We examined the association between the symptom-to-reperfusion-time and cardiovascular magnetic resonance (CMR)-derived global strain parameters and transmural infarct extent in ST-segment elevation myocardial infarction (STEMI) patients. Methods and results The study included 108 STEMI patients who underwent successful primary percutaneous coronary intervention (PPCI). Patients were categorized according to the median symptom-to-reperfusion-time: shorter (<160 min, n = 54) and longer times (>160 min, n = 54). CMR was performed 2–7 days after PPCI and at 1 month. CMR cine imaging was performed for functional assessment and late gadolinium enhancement to evaluate transmural infarct extent. Myocardial feature-tracking was used for strain analysis. Groups were comparable in relation to incidence of LAD disease and pre- and post-PPCI thrombolysis in myocardial infarction (TIMI) flow grades. The mean transmural extent score at follow-up was lower in patients with shorter reperfusion time (P < 0.01). Both baseline and follow-up maximum transmural extent scores were smaller in patients with shorter reperfusion time (P = 0.03 for both). Patients with shorter reperfusion time had more favourable global left ventricular (LV) circumferential strain (baseline, P = 0.049; follow-up, P = 0.01) and radial strain (baseline, P = 0.047; follow-up, P < 0.01), whilst LV longitudinal strain appeared comparable for both baseline and follow-up (P > 0.05 for both). In multi-variable regression analysis including all three strain directions, baseline LV circumferential strain was independently associated with the mean transmural extent score at follow-up (β=1.89, P < 0.001). Conclusion In STEMI patients, time-to-reperfusion was significantly associated with smaller transmural extent of infarction and better LV circumferential and radial strain. Moreover, infarct transmurality and residual LV circumferential strain are closely linked. [ABSTRACT FROM AUTHOR]

The kidney is a major target organ for the adverse effects of pharmaceuticals; renal tubular epithelial cells (TECs) are particularly vulnerable to drug‐induced toxicity. TECs have regenerative capacity; however, maladaptive repair of TECs after injury leads to renal fibrosis, resulting in chronic kidney disease (CKD). We previously reported the specific expression of CD44 in failed‐repair TECs of rat CKD model induced by ischemia reperfusion injury. Here, we investigated the pathophysiological role of CD44 in renal fibrogenesis in allopurinol‐treated rat CKD model. Dilated or atrophic TECs expressing CD44 in fibrotic areas were collected by laser microdissection and subjected to microarray analysis. Gene ontology showed that extracellular matrix (ECM)‐related genes were upregulated and differentiation‐related genes were downregulated in dilated/atrophic TECs. Ingenuity Pathway Analysis identified CD44 as an upstream regulator of fibrosis‐related genes, including Fn1, which encodes fibronectin. Immunohistochemistry demonstrated that dilated/atrophic TECs expressing CD44 showed decreases in differentiation markers of TECs and clear expression of mesenchymal markers during basement membrane attachment. In situ hybridization revealed an increase in Fn1 mRNA in the cytoplasm of dilated/atrophic TECs, whereas fibronectin was localized in the stroma around these TECs, supporting the production/secretion of ECM by dilated/atrophic TECs. Overall, these data indicated that dilated/atrophic TECs underwent a partial epithelial–mesenchymal transition (pEMT) and that CD44 promoted renal fibrogenesis via induction of ECM production in failed‐repair TECs exhibiting pEMT. CD44 was detected in the urine and serum of APL‐treated rats, which may reflect the expression of CD44 in the kidney. Maladaptive repair of renal tubular epithelial cells (TECs) leads to chronic kidney disease (CKD). Here, pathophysiological role of CD44 expressed in failed‐repair TECs in renal fibrogenesis was investigated using rat model of CKD with allopurinol. Overall results indicated that CD44 promoted renal fibrogenesis via induction of ECM production in failed‐repair TECs exhibiting partial epithelial–mesenchymal transition. CD44 was also detected in the urine and serum of rat model of CKD, indicating potential of CD44 as a CKD biomarker. [ABSTRACT FROM AUTHOR]

For the ischemic preconditioning (IPC) intervention, the accuracy of the protocol is paramount for mediating its possible ergogenic effects. However, the lack of standardization and widespread use of arbitrary cuff pressures (ranging from 130 to >300 mmHg) have been predominantly observed, potentially affecting the results and compromising the reproducibility of findings. Thus, the purpose of this study was to determine an appropriate cuff pressure during IPC. Seventeen healthy male participants were enrolled in the study. Anthropometric measurements were initially conducted, followed by systolic and diastolic blood pressure measurements. Subsequently, we determined the individual thigh occlusion pressure (TOP) for the right leg using a hand-held Doppler device. Based on these findings, we developed an estimation equation for TOP, considering the current brachial systolic blood pressure (SBP) values. We then conducted a retrospective analysis of its capacity to mediate occlusion. We observed the ability to estimate TOP using the equation (p = 0.01; ES: 0.86), presenting -6% superiority in absolute values for occlusion compared to direct measurement (TOP equation: 169.9 ± 9.1; TOP direct measured: 161.2 ± 11.1). However, TOP estimation was insufficient to produce complete occlusion in two out of 17 subjects (11.8%). In conclusion, the estimation of TOP incorporating SBP values may offer a valid and practical means for cuff administration during IPC protocols with potential to minimize adverse effects and maximize its positive effects. [ABSTRACT FROM AUTHOR]

BackgroundThyroid hormone (TH) appears to have a reparative action on the postinfarcted myocardium. This novel action was recently tested in a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair). The present study performed a post-hoc analysis of data from the ThyRepair study to provide further insights into the novel actions of TH on the human postischemic myocardium.MethodsData from 41 patients participating in the ThyRepair study (n = 20 placebo and n = 21 LT3) were included in the analysis. LT3 treatment started after stenting and continued intravenously for 48 h. All patients had cardiac magnetic resonance (CMR) at hospital discharge; left ventricular (LV) ejection fraction (LVEF%), LV end-diastolic volume index (LVEDVi; mL/m2), LV end-systolic volume index (LVESVi; mL/m2), infarct volume (IV), left ventricular mass index (LVMi) as edema index, and microvascular obstruction (MVO) were assessed. Patients were divided into two groups based on the median value of the IV: patients with IV ≤ 20% of the LV (group A) and patients with IV > 20% (group B). CMR measurements at discharge are expressed as mean ± SD.ResultsIn group A, the placebo and T3-treated groups had similar LVEF% (56.8 ± 10.2 vs. 52.2 ± 10.5), LVEDVi (90.9 ± 19.8 vs. 92.8 ± 14.5), and LVESVi (40.8 ± 18.2 vs. 44.9 ± 14.1) at discharge. In group B, LVEDVi and LVESVi were 112 ± 23.8 and 68.3 ± 21.5 for placebo vs. 91.8 ± 18.6 and 49.0 ± 14.0 for the T3-treated group, respectively, p < 0.05. LVEF% was significantly increased in the T3-treated group vs. placebo, 47.3 ± 6.5 vs. 39.9 ± 8.7, p < 0.05. In group B, CMR LVMi was lower in T3-treated patients vs. placebo but did not reach statistical significance (p = 0.1). MVO was 1.95 ± 2.2 in placebo vs. 0.84 ± 0.9 in the LT3-treated group, p = 0.15.ConclusionThe present study suggests that acute LT3 treatment may exert more favorable effects on the recovery of cardiac function in patients with large infarct size. Furthermore, it signals a potential effect of LT3 on myocardial edema and microvascular obstruction. These novel findings merit further investigation in large trials.

BackgroundContinuous investment and systematic evaluation of program accomplishments are required to achieve excellence in ST-segment elevation myocardial infarction (STEMI) care, especially in resource-limited settings. Therefore, this study evaluates the impact of problem-driven interventions on reperfusion use rate in a long-term operating STEMI network from a low- to middle-income country.MethodsThis is a healthcare improvement evaluation study of Salvador's public STEMI network in a quasi-experimental design, comparing data from 2009 to 2010 (pre-intervention) and 2019-2020 (post-intervention). There were evaluated all confirmed STEMI cases assisted in both periods. The interventions, implemented since 2017, included: expanding the support team, defining criteria to be a spoke, and initiating continuous education activities. The primary outcome was the rate of patients undergoing reperfusion, with secondary outcomes being time from door-to-ECG (D2E) and ECG-to-STEMI-team trigger (E2T).ResultsOver ten years, the network's coverage increased by 300,000 individuals, and expanded by 1,800 km2. A total of 885 records were analyzed, 287 in the pre-intervention group (182 men [63·4%]; mean [SD] age 62·1 [12·5] years) and 598 in the post-intervention group (356 men [59·5%]; mean [SD] age 61.9 [11·8] years). It was noticed a substantial increase in reperfusion delivery rate (90 [31%] vs. 431 [73%]; P = 001) and reductions in time from D2E (159 [83–340] vs. 29 [15–63], P = 001), and E2T (31 [21–44] vs. 16 [6–40], P = 001).ConclusionThe strategies adopted by Salvador's STEMI network were associated with significant improvements in the rate of patients undergoing reperfusion and in D2E and E2T. However, the mortality rate remains high.

Background Early clinical experience with the Tenzing 7 delivery catheter (T7, Route 92 Medical, San Mateo, CA, USA) demonstrates high success rates for intracranial delivery of large bore aspiration catheters. Its soft, flexible, tapered tip mitigates the “ledge effect” that may cause resistance when navigating neurovascular devices through tortuous internal carotid arteries (ICAs) or other arterial branch origin variants. This study aims to characterize T7 performance across ICAs with varying tortuosities. Methods A retrospective analysis was performed of prospectively collected data from patients with acute ischemic stroke treated with aspiration thrombectomy using T7 between January 2020 and July 2022 at 3 stroke centers. The ICA tortuosity index (TI) was derived from the ratio of actual to straight length measurements from anterior‐posterior and lateral projections during digital subtraction angiography. T7 success is defined as delivering the aspiration catheter to the face of the occlusion. Regression analysis between TI and T7 success was performed. Correlations were calculated between TI, ICA grading, puncture‐to‐reperfusion time, number of passes, and final modified Treatment in Cerebral Infarction score. Significance was P ≤$ \le $ 0.05. Results Of 107 patients meeting inclusion, median age was 69 (interquartile range 60–81) years, and most occlusions were in the M1 segment (73/107; 68.2%). T7 rate of success was 95.3% (102/107), and there was no association between TI and T7 technical success (P = 0.23). Greater TIs and cavernous ICA tortuosity grades were not correlated with worse intraprocedural outcomes (P>0.24). Conclusion In our multicenter experience, T7 performed well even in highly tortuous extracranial vasculature. Successful aspiration catheter delivery and intraprocedural performance were consistent irrespective of ICA tortuosity. Our findings support the use of T7 in aspiration endovascular thrombectomy for acute stroke for patients with tortuous extracranial vasculature.

Abstract Background The ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low- and high-dose propofol supplementation of the cardioplegia solution during adult cardiac surgery versus sham supplementation. This update presents the statistical analysis plan, detailing how the trial data will be analysed and presented. Outlined analyses are in line with the Consolidated Standards of Reporting Trials and the statistical analysis plan has been written prior to database lock and the final analysis of trial data to avoid reporting bias (following recommendations from the International Conference on Harmonisation of Good Clinical Practice). Methods/design ProMPT-2 is a multi-centre, blinded, parallel three-group randomised controlled trial aiming to recruit 240 participants from UK cardiac surgery centres to either sham cardioplegia supplementation, low dose (6 µg/ml) or high dose (12 µg/ml) propofol cardioplegia supplementation. The primary outcome is cardiac-specific troponin T levels (a biomarker of cardiac injury) measured during the first 48 h following surgery. The statistical analysis plan describes the planned analyses of the trial primary and secondary outcomes in detail, including approaches to deal with missing data, multiple testing, violation of model assumptions, withdrawals from the trial, non-adherence with the treatment and other protocol deviations. It also outlines the planned sensitivity analyses and exploratory analyses to be performed. Discussion This manuscript prospectively describes, prior to the completion of data collection and database lock, the analyses to be undertaken for the ProMPT-2 trial to reduce risk of reporting and data-driven analyses. Trial registration ISRCTN ISRCTN15255199. Registered on 26 March 2019.

Cardioprotection is defined as the intrinsic ability of cardiac tissue to withstand challenges like ischemia-reperfusion and different metabolic stresses. Initially observed through ischemic preconditioning, the scope of cardioprotection has expanded to include other inducers of cardioprotective signaling like hypoxia, temperature fluctuations, and many pharmacological agents, suggesting the existence of shared signaling pathways and protective cascades. So far, intracellular signaling factors contributing to cardioprotection include protein kinases, the reperfusion injury salvage kinase (RISK) pathway, the Survivor Activating Factor Enhancement (SAFE) pathway, hypoxia-inducible factor-1a (HIF1a), microRNAs, Connexin 43, and many others. These factors play roles in activating downstream signaling elements and protective genes, enhancing mitochondrial function, and regulating protein expression and cytosolic functions to confer cardioprotection. SUR2A, a regulatory subunit of sarcolemmal ATP-sensitive K+ (KATP) channels, autophagy and mitochondria are highlighted as crucial end-effectors, with mechanisms like regulation of the mitochondrial permeability transition pore and activation of KATP channels being pivotal for cardioprotection. Despite advances in understanding these pathways, many aspects of cardioprotection remain to be better understood. It is a particular challenge to further explore therapeutic potentials and, finally, develop clinically viable strategies for cardiac protection.

This review discusses ATP-sensitive potassium (KATP) channels, which connect intracellular energy metabolism to cellular electrical activity and play crucial roles in various physiological processes, particularly in the pancreas and cardiovascular system. KATP channels open when ATP levels decrease during metabolic stress, such as ischemia, helping to protect the heart from injury by maintaining membrane potential and preventing calcium overload. These channels are found in multiple cell types across the cardiovascular system, influencing vascular tone and cardiac excitability. The review highlights the need for further research into the specific expression of KATP channel subunits in humans and the consequences of ischemic events on their functionality. Additionally, it explores the interplay between glycolysis and KATP channels, suggesting that glycolytic ATP can modulate KATP channel activity while emphasizing the cardioprotective effects during ischemic events. The potential for KATP channel openers (KCOs) as therapeutic agents for ischemic heart disease is noted, particularly in improving outcomes in patients undergoing cardiac procedures. Challenges remain in developing specific KCOs with minimal side effects, but advances in precision medicine may enhance targeted therapies in the future. Overall, KATP channels represent promising targets for enhancing cardiovascular health.

Background: Gum arabic (GA) contains anti-oxidant and anti-inflammatory compounds and protects tissues. Objectives: The purpose of the present study was to investigate the protective effect of GA on the spinal cord’s motor neurons after ischemia-reperfusion (I-R) injury. Materials & Methods: Thirty-five male rats (Sprague-Dawley) were randomly divided into five groups: Intact, sham surgery, control (4 mL/kg distilled water+I/R), low-dose gum arabic (GA 1 g/kg+I-R), and high-dose gum arabic (GA 4 g/kg+I-R). In the experimental groups, oral gavages’ treatment was performed for 21 days before surgery. Three days after I-R, the rats were evaluated for neurological function, biochemical, and histological analysis. Results: The mean motor deficit index (MDI) in the GA groups versus the control group was significantly lower (P

Experimental medicine provides the scientific community with a plethora of information on therapeutic efficacy of probiotic strains. However, from the point of view of evidence-based medicine, the list of disorders controlled by probiotics is limited to antibiotic-associated diarrhea in adults and children, Clostridium difficile-associated diarrhea, acute infectious diarrhea in children and adults, eradication therapy, ulcerative colitis and irritable bowel syndrome. Recently, these indications are also amended by well-validated clinical guidelines for the usage of probiotic preparations, in order to modulate immunity. Given the permeability of gastrointestinal and immune system barriers for pathogenic and opportunistic microbiota, it seems logical to assume the effectiveness of probiotics as potential symbiotic regulators of nervous and cardiovascular systems. It should also be taken into account that metabolic disorders, e.g., obesity, with a low-intensity inflammatory response and characteristic cytokine pattern, are acquired as a gain of human civilization. In this regard, we propose a scientific hypothesis about the effectiveness of probiotic microbial strains in increasing myocardial resistance to ischemic-reperfusion injury, due to their ability to block individual links of the cytokine cascade during the development of inflammatory response, for its subsequent translation into clinical practice.The development and validation of a new experimental model of systemic inflammatory response syndrome (SIRS) in male Wistar rats, including obesity, acute inflammatory process of the colon, and antibiotic-induced dysbiosis, became basic to the study of efficacy of probiotic drugs in terms of myocardial resistance to ischemicreperfusion injury (IRI). Rats with SIRS showed a significantly increased size of the infarction area (+28%) upon experiments with isolated perfused heart under global ischemia-reperfusion conditions. Significant changes in the leukocyte formula and immunological parameters associated with SIRS were corrected by introduction of a mixture of probiotic strains L. acidophilus (LA-5) and B. animalis subsp. lactis (BB-12), and the isolated strain L. delbrueckii TS1-06. In both groups with probiotic correction, there was a decrease in the infarction area compared to the SIRS group. General and specific changes in IL-2, transforming growth factor-b (TGF-b) and tumor necrosis factor-a (TNFa) were noted. The reduction of myocardial infarction by probiotics may be related to the blocking of first-order cytokines, which leads to a «break» of proinflammatory cascade. A need for in-depth study of cardioprotective mechanisms mediated by probiotics was confirmed due to their potential usage as a symbiotic alternative to biological drugs which block the main pro-inflammatory cytokines.

在全球脑血管病医疗工作者的共同努力下，近年来脑血管病的诊疗取得了长足的进步。众多高质量的临床研究涵盖了脑血管病多个领域和热点，例如：缺血性卒中急性期取栓/溶栓，针对心房颤动的干预，血压管理等其他卒中急性期干预措施，为脑血管病的临床诊疗提供了扎实可靠的循证医学证据，并促进了脑血管病疾病负担的降低。本文对2023年脑血管病领域重要的临床研究进展进行回顾，帮助读者更好地了解这些临床研究的精华，并期待未来涌现出更多、更好的脑血管病临床研究。 Abstract: Cerebrovascular clinicians from different countries all over the world made great progress in the diagnosis and treatment of cerebral vascular diseases in recent years. Numerous high-quality clinical studies cover multiple fields and hotspots of cerebral vascular disease, such as thrombectomy/thrombolysis in the acute phase of ischemic stroke, intervention for atrial fibrillation, blood pressure management and other acute phase intervention measures, providing solid and reliable evidence-based medical evidence for clinical diagnosis and treatment in cerebral vascular disease, and promoting the reduction of cerebral vascular disease burden. This paper reviews the important clinical research progress in the field of cerebral vascular disease in 2023, helping readers better understand the advantages and great significance of these clinical studies, and looking forward to more and better cerebral vascular disease clinical studies in the future.

Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

ABSTRACTBackground and aims Hemodynamic instability during postreperfusion syndrome remains the most significant concern for transplantation teams. Various strategies have been investigated in an attempt to reduce the occurrence of postreperfusion in liver transplantation, including the use of mannitol as a scavenger of free radicals and inflammatory mediators. The study examined mannitol intraoperative antioxidant effect on reperfusion hemodynamic events during living donor liver transplantation (LDLT).Methodology This prospective randomized controlled trial divided 60 participants with end-stage liver disease into two groups of 30 participants each. The mannitol group was administered 1 g/kg of mannitol (20%) in a 500-mL labeled bottle (solution A); the control group received the same amount of normal saline (0.9%) in a 500-mL labeled bottle (solution B). The primary outcome was mean arterial pressure (MAP) postreperfusion. Secondary outcomes were recorded after reperfusion: cardiac output (COP), systemic vascular resistance (SVR), the amount of vasopressor administered, central venous pressure (CVP), and urine output (UOP). This study received ethics committee approval (R 42/2022) and was registered at clinicaltrials.gov (NCT05277623).Results The MAP parameters were significantly lower in the control group, with MAP

Background/Objectives: This study explores the effects of two probiotics, Lactobacillus helveticus R0052 and Bifidobacterium longum R0175, on myocardial infarction (MI) and associated depression-like behaviours, with a focus on sex differences. Methods: MI was induced in adult male and female rats by occluding the left anterior coronary artery for 30 min, followed by 24 h of reperfusion. Probiotics were administered via drinking water for at least two weeks before ischemia. Infarct size, plasma C-reactive protein (CRP), estradiol levels, and intestinal permeability were then measured. Two weeks after, MI subgroups of rats were tested for depression-like behaviours. Results: We found a significant interaction between sex and probiotics in relation to infarct size. Probiotics significantly reduced the infarct size compared to the vehicle group in female rats but not in males. Probiotics increased the plasma estradiol levels and reduced the CRP concentrations in females, suggesting anti-inflammatory and cardioprotective properties. Probiotics significantly increased intestinal resistance following MI in males only, suggesting sex-specific physiological responses to treatment. Probiotics enhanced social interaction in males with MI but not in females. Similarly, in the forced swim test, probiotics reduced immobility in males with MI but increased it in females, further underscoring the sex-dependent effects of probiotics. Conclusions: This study reports cardioprotective effects of probiotics upon MI in female rats, while benefits in male rats were rather at the behavioural level. These results highlight distinct physiological and behavioural responses between sexes, emphasizing the need to account for sex differences in future tests of probiotics as a prophylactic treatment for MI.