RESUMEN
AIMS: To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO). METHODS: 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG. RESULTS: A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1-4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes. CONCLUSION: The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.
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Electrorretinografía , Isquemia , Retina , Oclusión de la Vena Retiniana , Humanos , Oclusión de la Vena Retiniana/fisiopatología , Oclusión de la Vena Retiniana/diagnóstico , Electrorretinografía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedad Aguda , Isquemia/fisiopatología , Isquemia/diagnóstico , Retina/fisiopatología , Retina/diagnóstico por imagen , Agudeza Visual/fisiología , Adaptación a la Oscuridad/fisiología , AdultoRESUMEN
Chronic limb threatening ischemia (CLTI) poses a significant treatment challenge for vascular surgeons, interventionalists, podiatrists, and associated medical specialists. The evidence for what constitutes appropriate care is rapidly evolving and new treatment options are in constant development. This review examines the current guidelines for CLTI care, as well as reported outcomes for multiple care strategies in this patient population, including revascularization and medical optimization. We performed a literature review of the PubMed database, reviewing articles that reported outcomes for CLTI care between 2000 and 2023, and described these outcomes as they relate to the current state of CLTI treatment. Significant data are still forthcoming regarding CLTI care, but widespread adoption of appropriate CLTI care is essential for the treatment of this vulnerable population.
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Isquemia Crónica que Amenaza las Extremidades , Humanos , Resultado del Tratamiento , Factores de Riesgo , Isquemia Crónica que Amenaza las Extremidades/terapia , Procedimientos Quirúrgicos Vasculares/normas , Procedimientos Quirúrgicos Vasculares/efectos adversos , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/normas , Medicina Basada en la Evidencia/normas , Guías de Práctica Clínica como Asunto , Isquemia/terapia , Isquemia/diagnóstico , Isquemia/fisiopatología , Recuperación del Miembro , Enfermedad CrónicaRESUMEN
BACKGROUND: To examine the influence of liver function on patients with chronic limb-threatening ischemia (CLTI), we classified patients with CLTI after revascularization according to their modified albumin-bilirubin (ALBI) grades. METHODS: We retrospectively analyzed single-center data of patients who underwent revascularization for CLTI between 2015 and 2020. Patients were classified with ALBI grades 1, 2a, and 2b and 3 according to the ALBI score, which was calculated, based on serum albumin and total bilirubin levels. The endpoints were the 2-year amputation-free survival (AFS) and 1-year wound healing rates. RESULTS: We included 190 limbs in 148 patients, and 50, 54, and 86 cases were assigned as grade 1, 2a, and 2b and 3, respectively. The 2-year AFS rates for the grade 1, 2a, and 2b and 3 groups were 79 ± 6%, 66% ± 7%, and 45 ± 6%, respectively (P < 0.01). One-year cumulative wound healing rates for grade 1, 2a, and 2b and 3 groups were 68 ± 7%, 69% ± 6%, and 48% ± 5%, respectively (P = 0.01). Multivariate Cox proportional hazard analyses identified age (≥75 years), dependent ambulatory status, and modified ALBI grades 2b and 3 compared with grades 1 and 2a as significant independent predictors of AFS. The dependent ambulatory status and Wound, Ischemia, and foot Infection classification stage 4 were significant negative predictors of wound healing. CONCLUSIONS: Many patients with CLTI had high modified ALBI grades, and impaired liver function classified as modified ALBI grade 2b and 3 is a robust negative predictor of AFS.
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Amputación Quirúrgica , Bilirrubina , Biomarcadores , Recuperación del Miembro , Enfermedad Arterial Periférica , Valor Predictivo de las Pruebas , Albúmina Sérica Humana , Cicatrización de Heridas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Bilirrubina/sangre , Albúmina Sérica Humana/análisis , Biomarcadores/sangre , Factores de Tiempo , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Medición de Riesgo , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/cirugía , Isquemia Crónica que Amenaza las Extremidades/cirugía , Isquemia Crónica que Amenaza las Extremidades/sangre , Isquemia Crónica que Amenaza las Extremidades/diagnóstico , Isquemia Crónica que Amenaza las Extremidades/mortalidad , Resultado del Tratamiento , Supervivencia sin Progresión , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad , Pruebas de Función Hepática , Isquemia/sangre , Isquemia/diagnóstico , Isquemia/cirugía , Isquemia/fisiopatología , Isquemia/mortalidadRESUMEN
Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.
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Envejecimiento , Hiperemia , Microcirculación , Músculo Esquelético , Flujo Sanguíneo Regional , Espectroscopía Infrarroja Corta , Hiperemia/fisiopatología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Humanos , Estudios Retrospectivos , Masculino , Envejecimiento/metabolismo , Envejecimiento/fisiología , Anciano , Femenino , Adulto , Adulto Joven , Persona de Mediana Edad , Factores de Edad , Isquemia/fisiopatología , Isquemia/metabolismo , Oxígeno/sangre , Oxígeno/metabolismoRESUMEN
Critical Limb Ischemia or chronic limb-threatening ischemia represents the end stage of peripheral artery disease where arterial flow is compromised to the lower extremities and risk of limb loss may become imminent. Revascularization of lower extremities is one of the cornerstones of limb salvage and amputation prevention. Establishing centers of high quality CLI therapy requires creating different foundational pillars in order to be successful. This article discusses critical limb ischemia center creation from the perspective of critical limb ischemia therapists working in an outpatient setting.
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Isquemia , Recuperación del Miembro , Enfermedad Arterial Periférica , Humanos , Isquemia/terapia , Isquemia/fisiopatología , Isquemia/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Crítica , Atención Ambulatoria , Isquemia Crónica que Amenaza las Extremidades/cirugía , Instituciones de Atención Ambulatoria , Resultado del Tratamiento , Grupo de Atención al Paciente , Extremidad Inferior/irrigación sanguínea , Prestación Integrada de Atención de SaludRESUMEN
We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of ßIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.
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Modelos Animales de Enfermedad , Miembro Posterior , Isquemia , Músculo Esquelético , Animales , Ratas , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigación sanguínea , Miembro Posterior/irrigación sanguínea , Miembro Posterior/patología , Isquemia/patología , Isquemia/metabolismo , Isquemia/fisiopatología , Masculino , Ratas Wistar , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Tubulina (Proteína)/metabolismo , Enfermedad Arterial Periférica/patología , Enfermedad Arterial Periférica/metabolismo , Enfermedad Arterial Periférica/fisiopatologíaRESUMEN
BACKGROUND: In microvascular head and neck reconstruction, ischemia of the free flap tissue is inevitable during microsurgical anastomosis and may affect microvascular free flap perfusion, which is a prerequisite for flap viability and a parameter commonly used for flap monitoring. The aim of this study was to investigate the influence of the number of ischemia intervals and ischemia duration on flap perfusion. METHODS: Intraoperative and postoperative flap blood flow, hemoglobin concentration, and hemoglobin oxygen saturation at 2 and 8 mm tissue depths, as measured with the O2C tissue oxygen analysis system, were retrospectively analyzed for 330 patients who underwent microvascular head and neck reconstruction between 2011 and 2020. Perfusion values were compared between patients without (control patients) and with a second ischemia interval (early or late) and examined with regard to ischemia duration. RESULTS: Intraoperative and postoperative flap blood flow at 8 mm tissue depth were lower in patients with early second ischemia intervals than in control patients [102.0 arbitrary units (AU) vs 122.0 AU, P = .030; 107.0 AU vs 128.0 AU, P = .023]. Both differences persisted in multivariable analysis. Intraoperative and postoperative flap blood flow at 8 mm tissue depth correlated weakly negatively with ischemia duration in control patients (r = -.145, P = .020; r = -.124, P = .048). Both associations did not persist in multivariable analysis. CONCLUSIONS: The observed decrease in microvascular flap blood flow after early second ischemia intervals may reflect ischemia-related vascular flap tissue damage and should be considered as a confounding variable in flap perfusion monitoring.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Isquemia , Procedimientos de Cirugía Plástica , Humanos , Colgajos Tisulares Libres/irrigación sanguínea , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Neoplasias de Cabeza y Cuello/cirugía , Anciano , Isquemia/cirugía , Isquemia/fisiopatología , Microcirugia/métodos , Adulto , Factores de Tiempo , Flujo Sanguíneo Regional/fisiologíaRESUMEN
The neutral result of the PROMINENT trial has led to questions about the future for pemafibrate. This commentary discusses possible reasons for the lack of benefit observed in the trial. There were, however, indicators suggesting therapeutic potential in microvascular ischaemic complications associated with peripheral artery disease, with subsequent analysis showing reduction in the incidence of lower extremity ischaemic ulceration or gangrene. Reassurance about the safety of pemafibrate, together with emerging data from PROMINENT and experimental studies, also suggest benefit with pemafibrate in non-alcoholic fatty liver disease (alternatively referred to as metabolic dysfunction-associated steatotic liver disease) and microangiopathy associated with diabetes, which merit further study.
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Benzoxazoles , Butiratos , Animales , Humanos , Benzoxazoles/uso terapéutico , Benzoxazoles/efectos adversos , Butiratos/uso terapéutico , Butiratos/efectos adversos , Hipolipemiantes/uso terapéutico , Hipolipemiantes/efectos adversos , Isquemia/tratamiento farmacológico , Isquemia/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad Arterial Periférica/tratamiento farmacológico , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal "cellular-cocktail" prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI. METHODS: Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach. RESULTS: AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified. CONCLUSIONS: The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.).
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Tejido Adiposo , Modelos Animales de Enfermedad , Isquemia , Células Madre Mesenquimatosas , Ratones Endogámicos BALB C , Ratones Desnudos , Animales , Ratones , Isquemia/terapia , Isquemia/fisiopatología , Cordón Umbilical/citología , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Neovascularización Fisiológica , Células Endoteliales , HumanosRESUMEN
BACKGROUND: Considering a patient's anatomy and vascular conditions, aorto-femoral bypass is a treatment approach for the open repair of abdominal aortic aneurysms. This study aimed at evaluating changes in the remnant iliac artery and their correlation with the preservation state of retrograde flow from femoral anastomosis. METHODS: Of 221 patients who underwent abdominal aortic aneurysm surgery between 2007 and 2022 in Pusan National University Hospital, 29 patients who underwent aorto-femoral bypass were included in this retrospective cohort study. Of these patients, 21 underwent aortobifemoral bypass and 8 underwent aortoiliac-and-femoral bypass. The change in size of the iliac artery from preoperative to postoperative and whether this difference in size depended on the status of postoperative retrograde flow were investigated. Additionally, factors affecting overall mortality and ischemic complications were identified. RESULTS: The median duration from operation to the last follow-up was 2069.5 days (about 5.7 years). The average age of the patients was 78.1 years, and the proportion of males was 75.9%. In cases of disappearance of postoperative retrograde flow from the femoral anastomosis, the postoperative iliac artery size was significantly reduced compared to its preoperative size (18.4 ± 18.9 mm vs. 13.2 ± 7.9 mm, respectively; P = 0.04). The group with maintained retrograde flow had significantly larger residual common iliac artery size than the group with disappearance of flow. (20.0 ± 28.0 mm vs. 14.6 ± 8.5 mm, respectively; P = 0.02). Disappearance of retrograde flow was a significant factor in the iliac artery size reduction after surgery (odds ratio, 2.5; 95% confidence interval, 1.9-5.3; P = 0.02). Three patients with maintained retrograde flow (18.8%) required intervention owing to an increase in the size of the iliac artery. The factors that significantly influenced overall death as analyzed by Cox proportional hazard regression were chronic obstructive pulmonary disease (hazard ratio, 36.8; 95% confidence interval, 1.6-870.0; P = 0.03), peripheral arterial occlusive disease (hazard ratio, 12.7; 95% confidence interval, 1.4-115.8; P = 0.02), and disappearance of retrograde flow (hazard ratio, 8.7; 95% confidence interval, 1.2-63.9; P = 0.03). CONCLUSIONS: Among the open repair methods for abdominal aortic aneurysms, if retrograde flow was not maintained through femoral anastomosis when aorto-femoral bypass was performed, the size of the remaining iliac artery decreased. However, loss of retrograde flow increased long-term mortality. When aorto-femoral bypass is performed, regular imaging follow-up is necessary at appropriate intervals to check the remnant iliac artery and retrograde flow.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Arteria Femoral , Arteria Ilíaca , Flujo Sanguíneo Regional , Humanos , Masculino , Estudios Retrospectivos , Arteria Ilíaca/cirugía , Arteria Ilíaca/fisiopatología , Arteria Ilíaca/diagnóstico por imagen , Femenino , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/fisiopatología , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Arteria Femoral/cirugía , Arteria Femoral/fisiopatología , Arteria Femoral/diagnóstico por imagen , Anciano , Resultado del Tratamiento , Factores de Riesgo , Factores de Tiempo , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Implantación de Prótesis Vascular/instrumentación , Anciano de 80 o más Años , Hospitales Universitarios , Angiografía por Tomografía Computarizada , Isquemia/fisiopatología , Isquemia/cirugía , Isquemia/diagnóstico por imagen , Isquemia/etiología , Isquemia/mortalidad , Complicaciones Posoperatorias/etiología , Persona de Mediana EdadRESUMEN
BACKGROUND: Despite being in an oxygen-rich environment, endothelial cells (ECs) use anaerobic glycolysis (Warburg effect) as the primary metabolic pathway for cellular energy needs. PFKFB (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase)-3 regulates a critical enzymatic checkpoint in glycolysis and has been shown to induce angiogenesis. This study builds on our efforts to determine the metabolic regulation of ischemic angiogenesis and perfusion recovery in the ischemic muscle. METHODS: Hypoxia serum starvation (HSS) was used as an in vitro peripheral artery disease (PAD) model, and hind limb ischemia by femoral artery ligation and resection was used as a preclinical PAD model. RESULTS: Despite increasing PFKFB3-dependent glycolysis, HSS significantly decreased the angiogenic capacity of ischemic ECs. Interestingly, inhibiting PFKFB3 significantly induced the angiogenic capacity of HSS-ECs. Since ischemia induced a significant in PFKFB3 levels in hind limb ischemia muscle versus nonischemic, we wanted to determine whether glucose bioavailability (rather than PFKFB3 expression) in the ischemic muscle is a limiting factor behind impaired angiogenesis. However, treating the ischemic muscle with intramuscular delivery of D-glucose or L-glucose (osmolar control) showed no significant differences in the perfusion recovery, indicating that glucose bioavailability is not a limiting factor to induce ischemic angiogenesis in experimental PAD. Unexpectedly, we found that shRNA-mediated PFKFB3 inhibition in the ischemic muscle resulted in an increased perfusion recovery and higher vascular density compared with control shRNA (consistent with the increased angiogenic capacity of PFKFB3 silenced HSS-ECs). Based on these data, we hypothesized that inhibiting HSS-induced PFKFB3 expression/levels in ischemic ECs activates alternative metabolic pathways that revascularize the ischemic muscle in experimental PAD. A comprehensive glucose metabolic gene qPCR arrays in PFKFB3 silenced HSS-ECs, and PFKFB3-knock-down ischemic muscle versus respective controls identified UGP2 (uridine diphosphate-glucose pyrophosphorylase 2), a regulator of protein glycosylation and glycogen synthesis, is induced upon PFKFB3 inhibition in vitro and in vivo. Antibody-mediated inhibition of UGP2 in the ischemic muscle significantly impaired perfusion recovery versus IgG control. Mechanistically, supplementing uridine diphosphate-glucose, a metabolite of UGP2 activity, significantly induced HSS-EC angiogenic capacity in vitro and enhanced perfusion recovery in vivo by increasing protein glycosylation (but not glycogen synthesis). CONCLUSIONS: Our data present that inhibition of maladaptive PFKFB3-driven glycolysis in HSS-ECs is necessary to promote the UGP2-uridine diphosphate-glucose axis that enhances ischemic angiogenesis and perfusion recovery in experimental PAD.
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Modelos Animales de Enfermedad , Glucólisis , Miembro Posterior , Isquemia , Músculo Esquelético , Neovascularización Fisiológica , Fosfofructoquinasa-2 , Flujo Sanguíneo Regional , Animales , Fosfofructoquinasa-2/metabolismo , Fosfofructoquinasa-2/genética , Isquemia/metabolismo , Isquemia/genética , Isquemia/fisiopatología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Masculino , Ratones Endogámicos C57BL , Humanos , Enfermedad Arterial Periférica/metabolismo , Enfermedad Arterial Periférica/genética , Enfermedad Arterial Periférica/fisiopatología , Transducción de Señal , Glucógeno/metabolismo , Recuperación de la Función , Células Endoteliales/metabolismo , Células Endoteliales/enzimología , Ratones , Hipoxia de la Célula , Células CultivadasRESUMEN
BACKGROUND: The frequency of distal lower extremity bypass (LEB) for infrapopliteal critical limb threatening ischemia (IP-CLTI) has significantly decreased. Our goal was to analyze the contemporary outcomes and factors associated with failure of LEB to para-malleolar and pedal targets. METHODS: We queried the Vascular Quality Initiative infrainguinal database from 2003 to 2021 to identify LEB to para-malleolar or pedal/plantar targets. Primary outcomes were graft patency, major adverse limb events [vascular reintervention, above ankle amputation] (MALE), and amputation-free survival at 2 years. Standard statistical methods were utilized. RESULTS: We identified 2331 LEB procedures (1,265 anterior tibial at ankle/dorsalis pedis, 783 posterior tibial at ankle, 283 tarsal/plantar). The prevalence of LEB bypasses to distal targets has significantly decreased from 13.37% of all LEB procedures in 2003-3.51% in 2021 (P < 0.001). The majority of cases presented with tissue loss (81.25. Common postoperative complications included major adverse cardiac events (8.9%) and surgical site infections (3.6%). Major amputations occurred in 16.8% of patients at 1 year. Postoperative mortality at 1 year was 10%. On unadjusted Kaplan-Meier survival analysis at 2 years, primary patency was 50.56% ± 3.6%, MALE was 63.49% ± 3.27%, and amputation-free survival was 71.71% ± 0.98%. In adjusted analyses [adjusted for comorbidities, indication, conduit type, urgency, prior vascular interventions, graft inflow vessel (femoral/popliteal), concomitant inflow procedures, surgeon and center volume] conduits other than great saphenous vein (P < 0.001) were associated with loss of primary patency and increased MALE. High center volume (>5 procedures/year) was associated with improved primary patency (P = 0.015), and lower MALE (P = 0.021) at 2 years. CONCLUSIONS: Despite decreased utilization, open surgical bypass to distal targets at the ankle remains a viable option for treatment of IP-CLTI with acceptable patency and amputation-free survival rates at 2 years. Bypasses to distal targets should be performed at high volume centers to optimize graft patency and limb salvage and minimize reinterventions.
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Amputación Quirúrgica , Bases de Datos Factuales , Recuperación del Miembro , Extremidad Inferior , Enfermedad Arterial Periférica , Supervivencia sin Progresión , Insuficiencia del Tratamiento , Injerto Vascular , Grado de Desobstrucción Vascular , Humanos , Masculino , Femenino , Anciano , Factores de Tiempo , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/mortalidad , Factores de Riesgo , Persona de Mediana Edad , Estudios Retrospectivos , Extremidad Inferior/irrigación sanguínea , Injerto Vascular/efectos adversos , Injerto Vascular/mortalidad , Medición de Riesgo , Isquemia/cirugía , Isquemia/fisiopatología , Isquemia/mortalidad , Estados Unidos , Anciano de 80 o más Años , Enfermedad Crítica , ReoperaciónRESUMEN
BACKGROUND: Infra-popliteal interventions for chronic limb-threatening ischemia (CLTI) can be impacted by the morphology of the tibial vessels. The aim of this study was to examine the impact of a novel morphology-driven classification on the outcomes of isolated tibial intervention for CLTI. METHODS: A database of patients undergoing isolated tibial interventions for CLTI at a single center between 2010 and 2020 was retrospectively queried. Patients with isolated infra-popliteal disease were identified, and their anatomy was scored as present or absent for lesion calcification (1 point), target vessel diameter<3.0 mm (1 point), lesion length>300 mm (1 point), and poor pedal runoff score (1 point). Patients were then divided into 3 groups: low risk (0 or 1 points), moderate risk (2 points), and high risk (3 or 4 points). Intention to treat analysis by the patient was performed. Limb-based patency (the absence of reintervention, occlusion, critical stenosis [>70%], or hemodynamic compromise with ongoing symptoms of CLTI as it related to the patency of the preoperatively determined target artery pathway) was assessed. Patient-oriented outcomes of amputation-free survival (AFS; survival without major amputation) and freedom from major adverse limb events (MALE; above ankle amputation of the index limb or major reintervention: new bypass graft, jump/interposition graft revision) were evaluated. RESULTS: 1,607 patients (55% male, average age 60 years, 3,846 vessels) underwent tibial intervention for CLTI. The majority of the patients were diabetic and of Hispanic origin. Morphologically, 27%, 31%, and 42% of the vessels were categorized as low risk, moderate risk, and high risk, respectively. There was a significant worsening of the infra-popliteal Global Limb Anatomic Staging System (GLASS) grading as the morphological risk increased. The 30-day major adverse cardiac events (MACE) were equivalent across the groups and were under the stated objective performance goal (OPG) of ≤10%. In contrast, both the 30-day MALE and the 30-day major amputations were significantly different across the groups, with the low-risk group remaining under the OPG of ≤9% and ≤4%, respectively, while the moderate risk and high risk exceeded the goal threshold. For the OPG, freedom from MALE was 60 ± 5%, 46 ± 5%, and 22 ± 9% at 5 years for low-, moderate-, and high-risk groups, respectively (mean ± standard error of the mean; P = 0.008). Overall AFS was 55 ± 5%, 37 ± 6%, and 18 ± 7% at 5 years for low-, moderate-, and high-risk groups, respectively (mean ± standard error of the mean; P = 0.003). CONCLUSIONS: Tibial anatomic morphology impacts isolated tibial endovascular intervention with adverse morphology associated with poorer short- and long-term outcomes. Risk stratification based on anatomic predictors should be an additional consideration as one intervenes on infra-popliteal vessels for CLTI.
Asunto(s)
Amputación Quirúrgica , Isquemia Crónica que Amenaza las Extremidades , Bases de Datos Factuales , Recuperación del Miembro , Enfermedad Arterial Periférica , Arterias Tibiales , Grado de Desobstrucción Vascular , Humanos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Factores de Riesgo , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/cirugía , Arterias Tibiales/fisiopatología , Arterias Tibiales/diagnóstico por imagen , Arterias Tibiales/cirugía , Factores de Tiempo , Persona de Mediana Edad , Medición de Riesgo , Isquemia Crónica que Amenaza las Extremidades/cirugía , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Supervivencia sin Progresión , Anciano de 80 o más Años , Resultado del Tratamiento , Isquemia/fisiopatología , Isquemia/cirugía , Isquemia/diagnóstico por imagen , Isquemia/terapiaRESUMEN
BACKGROUND: The heparin-bonded expanded polytetrafluoroethylene (He-ePTFE) conduit is an option for patients requiring infrainguinal revascularization (iIR), but the risk of failure may be unpredictable, especially in cases with poor run-off. Intraoperative transit-time flow (TTF) provides an automated and quantitative analysis of flow and may serve as an adjunct evaluation during surgical revascularization. The aim of this study was to assess TTF in patients undergoing iIR with He-PTFE at 3 referral hospitals and to establish a predictive flow threshold for graft occlusion. METHODS: A prospective registry initiated in 2020 enrolled patients undergoing iIR using He-PTFE for critical limb ischemia or severe claudication, and TTF measurement was analyzed. Preoperative assessments of anatomical and clinical characteristics were available for all patients. The HT353 Optima Meter (Transonic Systems Inc., Ithaca, NY, USA) was used in all procedures according to a standardized protocol. The institutional ethics committee approved the study. A predictive model using receiver operating characteristic curve analysis was utilized to establish the threshold of flow, and variables were compared. Anatomical and clinical evaluation were reported according to Rutherford grade, Global Limb Anatomic System and Wound, Ischemia, and foot Infection classification. The main outcome considered was the correlation between TTF and graft occlusion. Secondary outcomes included survival, other predictors of graft occlusion, freedom from major adverse cardiovascular events, and freedom from major amputation. RESULTS: Among 68 patients, 55.8% had Rutherford 5-6, 45.6% had Global Limb Anatomic System 3 and 73.5% had Wound, Ischemia, and foot Infection 3-4. Distal anastomosis was at tibial level in 23.5% and mean diameter of conduit was 6.4 mm. Basal and postoperative TTF were 27.8 ± 15.6 ml/min and 109.0 ± 53.0 ml/min, respectively. After a mean follow-up of 18 ± 13 months, 7 (10.9%) patients presented graft occlusion and 5 (7.8%) required major amputation. TTF threshold = 80 ml/min revealed a sensitivity and specificity of 81.8% (95% confidence interval 48.2-97.7) and 80.7% (95% confidence interval 68.1-90.0) respectively, and it was selected as cut-off for graft occlusion. Freedom from graft occlusion in patients with TTF >80 ml/min vs. TTF ≤80 ml/min at 6, 12, and 24 months was 95.7% (standard error (SE) = 0.030) vs. 65.5% (SE = 0.115), 95.7% (SE = 0.030) vs. 58.9% (SE = 0.120) and 90.9% (SE = 0.054) vs. 51.6% (SE = 0.126), P = 0.0003. No statistical difference in primary patency, secondary patency and limb salvage was observed. At multivariate analysis, distal anastomosis at tibial vessel (odds ratio 8.50) and TTF ≤80 ml/min (odds ratio 9.39) were independent predictors of graft occlusion. CONCLUSIONS: These results suggest that TTF may serve as a valuable tool in the management of iIR. A TTF measurement of ≤80 ml/min should be regarded as a predictor of graft occlusion, prompting consideration of additional intraoperative maneuvers to enhance arterial flow. Caution should be exercised in patients requiring direct tibial artery revascularization, as it represents a predictor of failure independent of TTF levels. Larger cohorts of patients and longer follow-up periods are necessary to confirm these findings.
Asunto(s)
Implantación de Prótesis Vascular , Prótesis Vascular , Oclusión de Injerto Vascular , Heparina , Isquemia , Enfermedad Arterial Periférica , Politetrafluoroetileno , Valor Predictivo de las Pruebas , Diseño de Prótesis , Flujo Sanguíneo Regional , Sistema de Registros , Grado de Desobstrucción Vascular , Humanos , Masculino , Femenino , Anciano , Estudios Prospectivos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/efectos adversos , Heparina/administración & dosificación , Heparina/efectos adversos , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/diagnóstico por imagen , Factores de Tiempo , Factores de Riesgo , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Isquemia/fisiopatología , Isquemia/cirugía , Isquemia/diagnóstico , Isquemia/diagnóstico por imagen , Persona de Mediana Edad , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo , Materiales Biocompatibles Revestidos , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Enfermedad Crítica , Recuperación del Miembro , Insuficiencia del Tratamiento , Amputación Quirúrgica , Medición de Riesgo , Claudicación Intermitente/fisiopatología , Claudicación Intermitente/cirugía , Claudicación Intermitente/diagnóstico por imagen , Claudicación Intermitente/diagnósticoRESUMEN
BACKGROUND: This study aimed to analyze the clinical outcomes after revascularization for chronic limb-threatening ischemia (CLTI) in patients aged ≥ 80 years and < 80 years. METHODS: We retrospectively analyzed multicenter data of 789 patients who underwent infrainguinal revascularization for CLTI between 2015 and 2021. The end points were 2-year overall survival (OS), amputation-free survival (AFS), limb salvage (LS), and postoperative complications. RESULTS: A total of 90 patients aged ≥ 80 years and 200 patients aged < 80 years underwent bypass surgery (BSX), and 205 patients aged ≥ 80 years and 294 patients aged < 80 years underwent endovascular therapy (EVT). Before the propensity score matching, multivariate analyses showed that age ≥ 80 years, lower body mass index and serum albumin levels, nonambulatory status, and end-stage renal disease were independent risk factors for 2-year mortality in the BSX and EVT groups. After propensity score matching, the 2-year OS was better in the < 80 years cohort than in the ≥ 80 years cohort in both the BSX and EVT groups (P = 0.018 and P = 0.035, respectively). There was no difference in the 2-year LS rates between the < 80 years and the ≥ 80 years cohorts in both the BSX and EVT groups (P = 0.621 and P = 0.287, respectively). According to the number of risk factors, except for age ≥ 80 years, there was no difference in the 2-year AFS rates between the < 80 years and ≥ 80 years cohorts for the BSX and EVT groups with 0-1 risk factor (P = 0.957 and P = 0.655, respectively). However, the 2-year AFS rate was poor, especially in the ≥ 80 years cohort in the BSX with 2-4 risk factors (P = 0.015). The Clavien-Dindo ≥ IV complication rates tended to be higher in the ≥ 80 years cohort than in the < 80 years cohort only in the BSX with 2-4 risk factors (P = 0.056). CONCLUSIONS: Patients with CLTI aged ≥ 80 years had poorer OS than those aged < 80 years. However, there was no difference in LS between the ≥ 80 years and < 80 years cohorts in both the BSX and EVT groups. Although age ≥ 80 years was associated with poorer OS, patients with 0-1 risk factor may benefit from revascularization, including BSX, because no difference was observed in AFS or Clavien-Dindo ≥ IV complications.
Asunto(s)
Amputación Quirúrgica , Isquemia Crónica que Amenaza las Extremidades , Procedimientos Endovasculares , Recuperación del Miembro , Enfermedad Arterial Periférica , Complicaciones Posoperatorias , Humanos , Estudios Retrospectivos , Masculino , Anciano de 80 o más Años , Femenino , Factores de Riesgo , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/terapia , Factores de Tiempo , Factores de Edad , Anciano , Medición de Riesgo , Isquemia Crónica que Amenaza las Extremidades/cirugía , Isquemia Crónica que Amenaza las Extremidades/mortalidad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Supervivencia sin Progresión , Injerto Vascular/efectos adversos , Injerto Vascular/mortalidad , Resultado del Tratamiento , Isquemia/mortalidad , Isquemia/cirugía , Isquemia/terapia , Isquemia/fisiopatologíaRESUMEN
BACKGROUND: Pedal arch interrogation by ultrasound through systolic acceleration time measurement (Pedal Acceleration Time [PAT]) is a recently described technique that offers valuable insights into foot hemodynamics. Previous studies have demonstrated a correlation between PAT and the ankle-brachial index and PAT has been proposed as a prognostic tool for wound healing in patients with peripheral artery disease. This study aims to assess the correlation between PAT and Transcutaneous Pressure of Oxygen (TcPO2) in the diabetic foot population. METHODS: In this single-center cross-sectional study PAT and TcPO2 were measured in diabetic patients with ischemic foot ulcers. The assessment of wound status was performed between the 12th and 16th week after the first evaluation. The primary outcome was to assess the correlation between the values obtained for PAT and TcPO2. The secondary outcome was to establish a cut-off value for wound healing. RESULTS: Sixty limbs with ischemic foot ulcers were evaluated. The results showed a correlation between PAT and TcPO2 [F (1.52) = 16.928; R2 = 0.246; P < 0.001]. The receiver operating characteristics curve analysis showed an optimal cut-off value at PAT >186 ms for predicting a nonhealing ulcer with a 96% specificity (area under the curve = 0.774; confidence interval 0.648-0.872; P < 0.001). CONCLUSIONS: PAT showed a significant correlation with TcPO2 with high specificity to identify nonhealing foot ulcers due to insufficient foot perfusion with a potential prognostic value in the diabetic foot population.
Asunto(s)
Monitoreo de Gas Sanguíneo Transcutáneo , Pie Diabético , Valor Predictivo de las Pruebas , Cicatrización de Heridas , Humanos , Pie Diabético/fisiopatología , Pie Diabético/diagnóstico , Pie Diabético/terapia , Masculino , Femenino , Estudios Transversales , Anciano , Persona de Mediana Edad , Factores de Tiempo , Pie/irrigación sanguínea , Oxígeno/sangre , Flujo Sanguíneo Regional , Isquemia/fisiopatología , Isquemia/diagnóstico por imagen , Isquemia/diagnóstico , Isquemia/terapia , HemodinámicaRESUMEN
BACKGROUND: Against the technological advances in limb salvage, below-the-knee amputation (BKA) remains a common procedure. Although most elective BKA is classified as clean operation, the reported stump complication rate is much higher than predicted. Postoperative casting (PC) may reduce the number of these complications. The aim of this study was to compare the efficacy of elastic bandage with knee immobilizer (EBKI) and PC in BKA stump complications. METHODS: Retrospective cohort comparison design identified patients who underwent BKA between 2000 and 2023 for non-correctable critical limb ischemia (CLI), or excessive tissue loss secondary to CLI, infection, severe neuropathy, or the combination of these and stratified them into 2 cohorts based on their postoperative stump dressing: EBKI and PC. BKAs that were done for trauma or neoplastic processes were excluded. The primary outcome measures: wound healing in 6 weeks and length of stay (LOS). SECONDARY OUTCOME MEASURES: stump injury, infection, dehiscence, necrosis, number of higher-level amputations, knee contracture, and post-BKA mobility with Special Interest Group of Amputee Medicine score. RESULTS: One hundred sixteen patients with 122 limbs (52 EBKI and 70 PC) were found who met inclusion criteria and analyzed. The groups were comparable in demographics and comorbidities and preoperative variables, including mobility. The primary wound healing at 6 weeks was higher (P = 0.007); wound dehiscence (P = 0.01) and LOS (P = 0.006) was lower in the PC group compared to EBKI group. The PC group achieved higher Special Interest Group of Amputee Medicine mobility score and lower number of contractures developed compared to the EBKI group. CONCLUSIONS: Applying and maintaining PC to the BKA stump during the first month of healing reduced the incidence of stump complications, shortened the LOS, and improved postrehabilitation mobility results. We found no effect of PC on postoperative infections, stump necrosis, and higher-level amputations.
Asunto(s)
Muñones de Amputación , Amputación Quirúrgica , Moldes Quirúrgicos , Cicatrización de Heridas , Humanos , Estudios Retrospectivos , Masculino , Femenino , Amputación Quirúrgica/efectos adversos , Anciano , Muñones de Amputación/fisiopatología , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Tiempo , Moldes Quirúrgicos/efectos adversos , Tiempo de Internación , Factores de Riesgo , Anciano de 80 o más Años , Isquemia/fisiopatología , Isquemia/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
Deep venous arterialization (DVA) is a final option for limb salvage in patients with end stage arterial anatomy. We report a 66-year-old dialysis dependent male with forefoot gangrene, Rutherford class 6 chronic limb ischemia, who required a redo endovascular DVA. On initial presentation an angiogram was demonstrated a desert foot with absent tibial runoff to his bilateral lower extremities. After discussion, patient elected to trial DVA in hope of avoiding a major amputation. A hybrid DVA was performed using a Pioneer Plus and .018â³ Viabahn stents from the peroneal artery into the peroneal venous system; following this, the peroneal vein was anastomosed to the lesser saphenous vein via an open posterior approach at the ankle. 3 months later, a second DVA was performed by exposing the above knee popliteal artery and vein and creating an end-to-side anastomosis. Of note, the great saphenous vein was less than 2 mm in diameter and no arm vein was available due to history of prior fistulas in bilateral arms. Via the popliteal vein, the posterior tibial vein was selected and additional .018â³ Viabahn stents were deployed from the malleolus to the P2 segment of the popliteal vein. Three months after the second hybrid DVA, the patient's forefoot had healed after split thickness skin grafting. Continued patency is noted of the re-do hybrid DVA with minimal calf edema. Newer creative strategies are required for "No Option Chronic Limb Ischemia" which is becoming more relevant in diabetic and dialysis dependent patients. This case illustrates the potential to convert a deep venous arterialization to a superficial venous arterialization for improved venous outflow and wound healing.
Asunto(s)
Procedimientos Endovasculares , Isquemia , Recuperación del Miembro , Vena Poplítea , Vena Safena , Stents , Grado de Desobstrucción Vascular , Humanos , Masculino , Anciano , Resultado del Tratamiento , Isquemia/fisiopatología , Isquemia/diagnóstico por imagen , Isquemia/cirugía , Isquemia/etiología , Procedimientos Endovasculares/instrumentación , Vena Poplítea/fisiopatología , Vena Poplítea/diagnóstico por imagen , Vena Poplítea/cirugía , Vena Safena/trasplante , Vena Safena/diagnóstico por imagen , Vena Safena/fisiopatología , Diálisis Renal , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/cirugía , Reoperación , Enfermedad Crónica , GangrenaRESUMEN
AIMS: Proper arteriogenesis after tissue ischaemia is necessary to rebuild stable blood circulation; nevertheless, this process is impaired in type 2 diabetes mellitus (T2DM). Raptor is a scaffold protein and a component of mammalian target of rapamycin complex 1 (mTORC1). However, the role of the endothelial Raptor in arteriogenesis under the conditions of T2DM remains unknown. This study investigated the role of endothelial Raptor in ischaemia-induced arteriogenesis during T2DM. METHODS AND RESULTS: Although endothelial mTORC1 is hyperactive in T2DM, we observed a marked reduction in the expression of endothelial Raptor in two mouse models and in human vessels. Inducible endothelial-specific Raptor knockout severely exacerbated impaired hindlimb perfusion and arteriogenesis after hindlimb ischaemic injury in 12-week high-fat diet fed mice. Additionally, we found that Raptor deficiency dampened vascular endothelial growth factor receptor 2 (VEGFR2) signalling in endothelial cells (ECs) and inhibited VEGF-induced cell migration and tube formation in a PTP1B-dependent manner. Furthermore, mass spectrometry analysis indicated that Raptor interacts with neuropilin 1 (NRP1), the co-receptor of VEGFR2, and mediates VEGFR2 trafficking by facilitating the interaction between NRP1 and Synectin. Finally, we found that EC-specific overexpression of the Raptor mutant (loss of mTOR binding) reversed impaired hindlimb perfusion and arteriogenesis induced by endothelial Raptor knockout in high-fat diet fed mice. CONCLUSION: Collectively, our study demonstrated the crucial role of endothelial Raptor in promoting ischaemia-induced arteriogenesis in T2DM by mediating VEGFR2 signalling. Thus, endothelial Raptor is a novel therapeutic target for promoting arteriogenesis and ameliorating perfusion in T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2 , Células Endoteliales , Isquemia , Proteína Reguladora Asociada a mTOR , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Movimiento Celular , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/fisiopatología , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/patología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Miembro Posterior/irrigación sanguínea , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Isquemia/metabolismo , Isquemia/fisiopatología , Isquemia/genética , Isquemia/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Neovascularización Fisiológica , Flujo Sanguíneo Regional , Proteína Reguladora Asociada a mTOR/metabolismo , Proteína Reguladora Asociada a mTOR/genética , Proteína Reguladora Asociada a mTOR/deficiencia , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a hallmark of PE. We previously demonstrated a role for leptin in endothelial dysfunction in pregnancy in the absence of placental ischemia. We hypothesized that placental ischemia requires hyperleptinemia and endothelial mineralocorticoid receptor (ECMR) expression to induce PE-associated endothelial dysfunction in pregnant mice. We induced placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure in pregnant ECMR-intact (ECMR+/+) and ECMR deletion (ECMR-/-) mice at gestational day (GD) 13. ECMR+/+ RUPP pregnant mice also received concurrent leptin infusion via miniosmotic pump (0.9 mg/kg/day). RUPP increased blood pressure via radiotelemetry and decreased fetal growth in ECMR+/+ pregnant mice. Both increases in blood pressure and reduced fetal growth were abolished in RUPP ECMR-/- mice. Placental ischemia did not decrease endothelial-dependent relaxation to acetylcholine (ACh) but increased phenylephrine (Phe) contraction in mesenteric arteries of pregnant mice, which was ablated by ECMR deletion. Addition of leptin to RUPP mice significantly reduced ACh relaxation in ECMR+/+ pregnant mice, accompanied by an increase in soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio. In conclusion, our data indicate that high leptin levels drive endothelial dysfunction in PE and that ECMR is required for clinical characteristics of hypertension and fetal growth restriction in placental ischemia PE. Collectively, we show that both ECMR and leptin play a role to mediate PE.NEW & NOTEWORTHY Leptin is a key feature of preeclampsia that initiates vascular endothelial dysfunction in preeclampsia characterized by placental ischemia. Endothelial mineralocorticoid receptor (ECMR) deletion in placental ischemia protects pregnant mice from elevations in blood pressure and fetal growth restriction in pregnancy. Increases in leptin production mediate the key pathological feature of endothelial dysfunction in preeclampsia in rodents. ECMR activation contributes to the increase in blood pressure and fetal growth restriction in preeclampsia.