RESUMEN

Background: We conducted a post-hoc analysis of the RICAMIS trial to investigate the effect of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) on the efficacy of remote ischemic conditioning treatment. Methods: In this post-hoc analysis, NLR, PLR, and SII were measured before randomization. Patients were divided into two groups based on their cut-off values: high vs low NLR, high vs low PLR, and high vs low SII groups. Each group was further subdivided into RIC and control groups. The primary endpoint was a poor outcome (mRS 2-6 at 90 days). Differences in the primary endpoint between the RIC and control subgroups were compared, and the interactions of treatment assignment with NLR, PLR, and SII were evaluated. Results: A total of 1679 patients were included in the final analysis. Compared with the control group, RIC significantly improved functional outcomes regardless of the inflammation status. The improved probability of poor outcome in the RIC vs control group was numerically greater in the high vs low inflammation group (NLR, 7.8% vs 5.1%; PLR, 7% vs 6.5%; SII, 9% vs 5.3%). However, we did not find an interaction effect of an intervention (RIC or control) with different NLR, PLR, or SII on clinical outcomes (P > 0.05). In addition, the NLR and SII were independently associated with functional outcomes in all patients, regardless of whether they received RIC. Conclusion: Inflammation may not affect the efficacy of RIC in patients with acute moderate ischemic stroke, although a lower probability of poor outcome at 90 days was identified in patients with a high vs low inflammatory status.

RESUMEN

INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. METHODS: The survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. RESULTS: A total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. CONCLUSIONS: Pharmacologic interactions result in major uncertainty about cytoprotective treatment choices.

Asunto(s)

Toma de Decisiones Clínicas , Fibrinolíticos , Accidente Cerebrovascular Isquémico , Pautas de la Práctica en Medicina , Terapia Trombolítica , Humanos , Masculino , Persona de Mediana Edad , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Terapia Trombolítica/efectos adversos , Pautas de la Práctica en Medicina/tendencias , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Incertidumbre , Trombectomía/efectos adversos , Encuestas de Atención de la Salud , Procedimientos Endovasculares/efectos adversos , Resultado del Tratamiento , Adulto , Factores de Tiempo , Fármacos Neuroprotectores/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/fisiopatología

RESUMEN

Systolic blood pressure variability (SBPV) is associated with outcome in acute ischemic stroke. Remote ischemic conditioning (RIC) has been demonstrated to be effective in stroke and may affect blood pressure. Relationship between SBPV and RIC treatment after stroke warrants investigation. A total of 1707 patients from per-protocol analysis set of RICAMIS study were included. The SBPV was calculated based on blood pressure measured at admission, Day 7, and Day 12. (I) To investigate the effect of SBPV on efficacy of RIC in stroke, patients were divided into High and Low categories in each SBPV parameter. Primary outcome was excellent functional outcome at 90 days. Compared with Control, efficacy of RIC in each category and interaction between categories were investigated. (II) To investigate the effect of RIC treatment on SBPV, SBPV parameters were compared between RIC and Control groups. Compared with Control, a higher likelihood of primary outcome in RIC was found in high category (max-min: adjusted risk difference [RD] = 7.2, 95% CI 1.2-13.1, P = 0.02; standard deviation: adjusted RD = 11.5, 95% CI 1.6-21.4, P = 0.02; coefficient of variation: adjusted RD = 11.2, 95% CI 1.4-21.0, P = 0.03). Significant interaction of RIC on outcomes were found between High and Low standard deviations (adjusted P < 0.05). No significant difference in SBPV parameters were found between treatment groups. This is the first report that Chinese patients with acute moderate ischemic stroke and presenting with higher SBPV, who were non-cardioemoblic stroke and not candidates for intravenous thrombolysis or endovascular therapy, would benefit more from RIC with respect to functional outcomes at 90 days, but 2-week RIC treatment has no effect on SBPV during hospital.

Asunto(s)

Presión Sanguínea , Precondicionamiento Isquémico , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Presión Sanguínea/fisiología , Anciano , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Persona de Mediana Edad , Precondicionamiento Isquémico/métodos , Resultado del Tratamiento , Sístole/fisiología

RESUMEN

BACKGROUND: Remote ischemic conditioning (RIC) is considered a promising non-pharmacological therapeutic strategy to mitigate ischemic injury. Although the precise mechanisms of RIC's protective effects remain elusive, existing data suggest that exosomes contribute significantly to these processes through cell-to-cell communication OBJECTIVE: This review aims to elucidate the role of exosomes in RIC-mediated multi-organ protection. METHODS: We systematically searched multiple databases through October 2023 for preclinical studies evaluating the effect of exosomes in ischemic models using RIC procedures. Key outcomes, such as improved organ function and reduced infarct size, were recorded. Articles were selected and data were extracted by independent pairs of reviewers. FINDINGS: A total of 16 relevant studies were identified in this review, showing that circulating exosomes derived from the plasma of RIC-treated animals exhibited protective effects akin to those of the RIC procedure itself. Exosome concentrations were measured in eight studies, six of which reported significant increases in the RIC group. Additional findings indicated that RIC might primarily modulate the expression of miRNAs and bioactive molecules delivered by exosomes, rather than directly altering circulating exosome levels. Notably, the expression of 11 distinct exosomal miRNAs was altered after RIC intervention, potentially involving multiple pathways. CONCLUSION: Exosomes appear to play a pivotal role in the protective effects induced by RIC. Clarifying their function in RIC under different pathological situations represents a grand challenge for future research.

Asunto(s)

Exosomas , Precondicionamiento Isquémico , Exosomas/metabolismo , Animales , Precondicionamiento Isquémico/métodos , Humanos , MicroARNs/metabolismo , MicroARNs/genética , MicroARNs/sangre , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo

RESUMEN

BACKGROUND: Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes. METHODS: Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1. RESULTS: Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13-75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14-3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23-1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30-1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73-1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61-1.56, P = 0.93). CONCLUSIONS: It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336565.

Asunto(s)

Precondicionamiento Isquémico , Trasplante de Riñón , Ensayos Clínicos Controlados Aleatorios como Asunto , Trasplante de Riñón/mortalidad , Humanos , Precondicionamiento Isquémico/métodos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/mortalidad , Rechazo de Injerto/mortalidad , Rechazo de Injerto/prevención & control , Funcionamiento Retardado del Injerto

RESUMEN

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

RESUMEN

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies.

Asunto(s)

Modelos Animales de Enfermedad , Accidente Cerebrovascular , Animales , Accidente Cerebrovascular/diagnóstico por imagen , Ratones , Masculino , Imagen de Perfusión/métodos , Arterias Cerebrales/diagnóstico por imagen , Ratones Endogámicos C57BL , Albúminas/química , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Espectroscopía Infrarroja Corta/métodos , Circulación Colateral

RESUMEN

Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and cardiac dysfunction, collectively termed stroke-heart syndrome (SHS). These cardiac alterations typically peak within 72 h of stroke onset and can have long-term effects on cardiac function. Post-stroke cardiac complications seriously affect prognosis and are the second most frequent cause of death in patients with stroke. Although traditional vascular risk factors contribute to SHS, other potential mechanisms indirectly induced by stroke have also been recognized. Accumulating clinical and experimental evidence has emphasized the role of central autonomic network disorders and inflammation as key pathophysiological mechanisms of SHS. Therefore, an assessment of post-stroke cardiac dysautonomia is necessary. Currently, the development of treatment strategies for SHS is a vital but challenging task. Identifying potential key mediators and signaling pathways of SHS is essential for developing therapeutic targets. Therapies targeting pathophysiological mechanisms may be promising. Remote ischemic conditioning exerts protective effects through humoral, nerve, and immune-inflammatory regulatory mechanisms, potentially preventing the development of SHS. In the future, well-designed trials are required to verify its clinical efficacy. This comprehensive review provides valuable insights for future research.

Asunto(s)

Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Cardiopatías/etiología , Cardiopatías/fisiopatología , Cardiopatías/terapia , Síndrome

RESUMEN

Background: Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation if applied early to patients with intracerebral hemorrhage (ICH). We hypothesize that early RIC, delivered for seven days in patients with spontaneous ICH, may reduce PHE growth. Methods: ICH patients presenting within 6 h of symptom onset and hematoma volume < 60 milliliters (mL) were randomized to an RIC + standard care or standard care (SC) group. The primary outcome measure was calculated edema extension distance (EED), with the cm assessed on day seven. Results: Sixty patients were randomized with a mean ± SD age of 57.5 ± 10.8 years, and twenty-two (36.7%) were female. The relative baseline median PHE were similar (RIC group 0.75 (0.5-0.9) mL vs. SC group 0.91 (0.5-1.2) mL, p = 0.30). The median EEDs at baseline were similar (RIC group 0.58 (0.3-0.8) cm vs. SC group 0.51 (0.3-0.8) cm, p = 0.76). There was no difference in the median day 7 EED (RIC group 1.1 (0.6-1.2) cm vs. SC group 1 (0.9-1.2) cm, p = 0.75). Conclusions: Early RIC therapy delivered daily for seven days was feasible. However, no decrease in EED was noted with the intervention.

RESUMEN

BACKGROUND: Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation. METHODS: A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor). RESULTS: Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P < 0.0001, I2 = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses. CONCLUSION: In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC. TRIAL REGISTRATION: This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).

Asunto(s)

Funcionamiento Retardado del Injerto , Precondicionamiento Isquémico , Trasplante de Riñón , Humanos , Trasplante de Riñón/métodos , Precondicionamiento Isquémico/métodos , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Rechazo de Injerto/prevención & control

RESUMEN

INTRODUCTION: Despite the appearance of off-pump coronary artery bypass grafting (CABG), ischemia-reperfusion injury (IRI) in the perioperative period still arouses concerns of clinicians. Remote ischemic conditioning (RIC) is the process of repeated ischemia and reperfusion in the peripheral vessels, which is proven to reduce IRI in vital organs. However, the effect of RIC in patients undergoing off-pump CABG is still unclear. METHODS: This IMPROVE trial is a national, multicenter, randomized, controlled, open-label, blinded-endpoint clinical trial designed to assess whether RIC intervention can improve short-term prognosis of patients undergoing off-pump CABG. It plans to enroll 648 patients who will be randomly assigned into a RIC group or control group. Patients in the RIC group will receive four cycles of 5 min of pressurization (about 200 mmHg) and 5 min of rest in the 3 days before and 7 days after the surgery. PLANNED OUTCOMES: The primary outcome is the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) within the 3-month follow-up. MACCE is defined as all-cause death, myocardial infarction, stroke, and coronary revascularization surgery. CLINICAL TRIAL REGISTRATION: NCT06141525 (ClinicalTrials.gov).

Asunto(s)

Puente de Arteria Coronaria Off-Pump , Humanos , Puente de Arteria Coronaria Off-Pump/métodos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Precondicionamiento Isquémico/métodos , Adulto , Resultado del Tratamiento

RESUMEN

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.

Asunto(s)

Arteriosclerosis Intracraneal , Accidente Cerebrovascular Isquémico , Adulto , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/terapia , Isquemia , Hemodinámica , Glucosa

RESUMEN

PURPOSE OF REVIEW: To provide an overview of (a) protective effects on mitochondria induced by remote ischemic conditioning (RIC) and (b) mitochondrial damage caused by anticancer therapy. We then discuss the available results of studies on mitochondrial protection via RIC in anticancer therapy-induced cardiotoxicity. RECENT FINDINGS: In three experimental studies in healthy mice and pigs, there was a RIC-mediated protection against anthracycline-induced cardiotoxicity and there was some evidence of improved mitochondrial function with RIC. The RIC-mediated protection was not confirmed in the two available studies in cancer patients. In adult cancer patients, RIC was associated with an adverse outcome. There are no data on mitochondrial function in cancer patients. Studies in tumor-bearing animals are needed to determine whether RIC does not interfere with the anticancer properties of the drugs and whether RIC actually improves mitochondrial function, ultimately resulting in improved cardiac function.

Asunto(s)

Antineoplásicos , Cardiotoxicidad , Mitocondrias Cardíacas , Cardiotoxicidad/prevención & control , Humanos , Animales , Antineoplásicos/efectos adversos , Mitocondrias Cardíacas/efectos de los fármacos , Precondicionamiento Isquémico Miocárdico/métodos , Neoplasias/tratamiento farmacológico

RESUMEN

BACKGROUND: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke. METHODS AND RESULTS: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P=0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P=0.05). CONCLUSIONS: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Asunto(s)

Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Isquemia Encefálica/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento

RESUMEN

Remote ischemic conditioning (RIC) is a therapeutic strategy to protect a vital organ like the brain from ischemic injury through brief and repeat cycles of ischemia and reperfusion in remote body parts such as arm or leg. RIC has been applied in different aspects of the stroke field and has shown promise. This narrative review will provide an overview of how to implement RIC in stroke patients, summarize the clinical evidence of RIC on stroke recovery, and discuss unresolved questions and future study directions.

Asunto(s)

Isquemia , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Encéfalo

RESUMEN

AIMS: Alzheimer's disease (AD) is a significant global health concern, and it is crucial that we find effective methods to prevent or slow down AD progression. Recent studies have highlighted the essential role of blood vessels in clearing Aß, a protein that contributes to AD. Scientists are exploring blood biomarkers as a potential tool for future AD diagnosis. One promising method that may help prevent AD is remote ischemic conditioning (RIC). RIC involves using sub-lethal ischemic-reperfusion cycles on limbs. However, a comprehensive understanding of how RIC can prevent AD and its long-term effectiveness is still lacking. Further research is essential to fully comprehend the potential benefits of RIC in preventing AD. METHODS: Female wild-type (WT) and APP/PS1 transgenic rats, aged 12 months, underwent ovariectomy and were subsequently assigned to WT, APP/PS1, and APP/PS1 + RIC groups. RIC was conducted five times a week for 4 weeks. The rats' depressive and cognitive behaviors were evaluated using force swimming, open-field tests, novel objective recognition, elevated plus maze, and Barnes maze tests. Evaluation of the neurovascular unit (NVU), synapses, vasculature, astrocytes, and microglia was conducted using immunofluorescence staining (IF), Western blot (WB), and transmission electron microscopy (TEM). Additionally, the cerebro-vasculature was examined using micro-CT, and cerebral blood flow (CBF) was measured using Speckle Doppler. Blood-brain barrier (BBB) permeability was determined by measuring the Evans blue leakage. Finally, Aß levels in the rat frontal cortex were measured using WB, ELISA, or IF staining. RESULTS: RIC enhanced memory-related protein expression and rescued depressive-like behavior and cognitive decline in APP/PS1 transgenic rats. Additionally, the intervention protected NVU in the rat frontal cortex, as evidenced by (1) increased expression of TJ (tight junction) proteins, pericyte marker PDGFRß, and glucose transporter 1 (GLUT1), as well as decreased VCAM1; (2) mitigation of ultrastructure impairment in neuron, cerebral vascular, and astrocyte; (3) upregulation of A2 astrocyte phenotype markers and downregulation of A1 phenotype markers, indicating a shift toward a healthier phenotype. Correspondingly, RIC intervention alleviated neuroinflammation, as evidenced by the decreased Iba1 level, a microglia marker. Meanwhile, RIC intervention elevated CBF in frontal cortex of the rats. Notably, RIC intervention effectively suppressed Aß toxicity, as demonstrated by the enhancement of α-secretase and attenuation of ß-secretase (BACE1) and γ- secretase and Aß1-42 and Aß1-40 levels as well. CONCLUSION: Chronic RIC intervention exerts vascular and neuroprotective roles, suggesting that RIC could be a promising therapeutic strategy targeting the BBB and NVU during AD development.

Asunto(s)

Enfermedad de Alzheimer , Disfunción Cognitiva , Ratones , Ratas , Femenino , Animales , Barrera Hematoencefálica/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Ratones Transgénicos , Ratas Transgénicas , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Ácido Aspártico Endopeptidasas/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/terapia , Modelos Animales de Enfermedad , Presenilina-1/genética , Presenilina-1/metabolismo

RESUMEN

BACKGROUND: Acute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI. METHODS: Subjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks. RESULTS: Eighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006). CONCLUSIONS: Among patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days. TRIAL REGISTRATION: URL: www. CLINICALTRIALS: gov . Unique identifier: NCT03868007. Registered 8 March 2019.

Asunto(s)

Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/terapia , Método Doble Ciego , Resultado del Tratamiento , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia

RESUMEN

RICAMIS (ClinicalTrials.gov Identifier: NCT03740971) trial has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke, but whether baseline NIHSS score can affect outcomes in stroke remains unclear. We conducted a post hoc analysis of RICAMIS to investigate the issue. Patients included in RICAMIS were divided into three groups based on baseline NIHSS score. The primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0-1. Compared with patients receiving usual care, we investigated association of RIC effect with outcomes in each group and interaction between RIC effect and stroke severity. Among 1776 patients, 1255 were assigned into NIHSS score 6-8 group, 402 into NIHSS score 9-12 group, and 119 into NIHSS score 13-16 group. A higher proportion of primary outcome was found associated with RIC in NIHSS score 9-12 group (adjusted risk difference [RD], 14.6 â€‹%; 95 â€‹% CI, 5.0 â€‹%-24.2 â€‹%; P â€‹= â€‹0.003), but no significant association was found in NIHSS score 6-8 group (adjusted RD, 2.3 â€‹%; 95 â€‹% CI, -2.5 â€‹%-7.2 â€‹%; P â€‹= â€‹0.34), or in NIHSS score 13-16 group (adjusted RD, 9.7 â€‹%; 95 â€‹% CI, -7.5 â€‹%-26.9 â€‹%; P â€‹= â€‹0.27). There was a significant interaction between RIC effect and stroke severity when analysis was performed between NIHSS score 6-8 and 9-12 groups (P â€‹= â€‹0.04), but not between NIHSS score 9-12 and 13-16 groups (P â€‹= â€‹0.57). Current study firstly reported patients with NIHSS score 9-12 may get more benefit from RIC after stroke with respect to excellent functional outcome at 90 days.

Asunto(s)

Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/terapia , Isquemia Encefálica/terapia , Isquemia Encefálica/complicaciones , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento

RESUMEN

BACKGROUND: Ischemic conditioning-induced cardioprotection was attenuated by dyslipidemia in some animal and clinical studies, which is not investigated in patients with stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to investigate the association of dyslipidemia on admission with the efficacy of remote ischemic conditioning (RIC). METHODS AND RESULTS: In this analysis, eligible patients were divided into dyslipidemia and normal-lipid groups according to the levels of 4 blood lipid profiles (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), which were further subdivided into RIC and control subgroups. We analyzed the differences in functional outcome between RIC and control subgroups in dyslipidemia and normal-lipid patients, respectively, and the interaction effects of RIC treatment with blood lipid levels were evaluated. Among 1776 patients from intention-to-treat analysis, 1419 patients with data of blood lipid profiles were included in the final analysis. A significantly higher proportion of modified Rankin Scale score 0 to 1 was identified in the RIC versus control subgroup across the normal-total cholesterol group (69.9% versus 63.5%; P=0.04), normal-triglycerides group (68.1% versus 60.5%; P=0.016), high-low-density lipoprotein cholesterol group (65.7% versus 57.7%; P=0.025), and normal-high-density lipoprotein cholesterol group (68.3% versus 60.5%; P=0.005). Similar statistical trends were found in the high-total cholesterol group (62.8% versus 55.5%; P=0.059), high-triglycerides group (67.8% versus 60.1%; P=0.099), normal-low-density lipoprotein cholesterol group (69.8% versus 63.7%; P=0.105), but no statistical significance was found in the low-high-density lipoprotein cholesterol group (63.4% versus 61%; P=0.705). Furthermore, no significant interaction effect of RIC intervention by blood lipid profiles was found. Similar results were obtained for lipids as continuous variables. CONCLUSIONS: Blood lipids on admission was not associated with the neuroprotective effect of RIC.

Asunto(s)

Dislipidemias , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/complicaciones , Isquemia/complicaciones , Lípidos , Triglicéridos , Colesterol , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Lipoproteínas HDL , Lipoproteínas LDL

RESUMEN

AIMS: A post hoc analysis of RICAMIS trial to evaluate functional outcomes in relation to patient age. METHODS: Patients in RICAMIS were divided into six age groups. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0-1. Compared with patients receiving usual care alone, we investigated the association of remote ischemic conditioning (RIC) effect with functional outcomes in each group and the interaction between RIC effect and age. RESULTS: Of 1776 patients, 498 were assigned to <60 years, 326 to 60 to <65 years, 325 to 65 to <70 years, 278 to 70 to <75 years, 206 to 75 to <80 years, and 143 to ≥80 years. Higher proportions of primary outcome were found associated with RIC in <60 years group (72.6% vs. 64.8%; adjusted risk difference [RD], 6.8%; 95% CI, -1.6% to 15.1%; p = 0.11), 60 to <65 years group (70.7% vs. 67.1%; adjusted RD, 3.1%; 95% CI, -7.2% to 13.3%; p = 0.56), 65 to <70 years group (70.5% vs. 63.6%; adjusted RD, 3.5%; 95% CI, -6.8% to 13.8%; p = 0.51), 70 to <75 years group (59.7% vs. 54.9%; adjusted RD, 4.7%; 95% CI, -7.1% to 16.4%; p = 0.61), 75 to <80 years group (61.5% vs. 55.9%; adjusted RD, 5.7%; 95% CI, -7.8% to 19.1%; p = 0.41), and ≥ 80 years group (59.2% vs. 59.7%; adjusted RD, -2.6%; 95% CI, -18.8% to 13.5%; p = 0.75). No significant interaction between RIC effect and age was found among groups. CONCLUSIONS: This is the first report that RIC effect may be attenuated with increasing age in patients with acute moderate ischemic stroke with respect to functional outcome.

Asunto(s)

Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Resultado del Tratamiento