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BACKGROUND: We evaluate the relationship between the hospital case volume (HCV) and mortality outcomes after open aortic repair (OAR) and endovascular aortic repair (EVAR) of intact (iEVAR) and ruptured (rEVAR) abdominal aortic aneurysm (AAA) using a contemporary administrative database. METHODS: The Healthcare Cost and Utilization Project Database for New York (2016) and New Jersey/Maryland/Florida (2016-2017) were queried using International Classification of Disease-10th edition to identify patients who had undergone OAR and EVAR. The hospitals were categorized into quartiles (Q) per overall (EVAR + OAR) volume, OAR-alone volume and EVAR-alone volume. Cox regression adjusted for confounding factors was used to estimate hazard ratios (HRs) for mortality. RESULTS: A total of 8,825 patients (mean age, 73.5 ± 9.5 years; 6,861 male [77.7%]) had undergone 1,355 OARs and 7,470 EVARs. Overall HCV had no impact on in-hospital mortality across quartiles after (iEVAR) (range, 0.7%-1.4%, P = 0.15), (rEVAR) (range, 20.5%-29.6%, P = 0.63) and open repair of intact AAA (iOAR) (range, 4.9%-8.8%, P = 0.63). However, the mortality rates after open repair of ruptured AAA (rOAR) in highest-volume (Q4) hospitals were significantly lower than those in the 3 lower quartile hospitals (23.1% vs. 44.7%, P < 0.001). When analyzed per OAR-alone volume, the same findings were observed (22.0% for Q4 vs. 41.6% for Q1-3, P < 0.001). Furthermore, in Q4 hospitals per the OAR-alone volume analysis, the mortality hazard was greater for rEVAR (39.0%) than for rOAR (22.0%) (HR = 2.3, 95% confidence interval, 1.02-5.34, P < 0.05). CONCLUSIONS: The mortality rates for iEVAR, rEVAR and iOAR were independent of HCV. However, after rOAR, mortality rates in high OAR volume hospitals were lower than those in the lower quartile hospitals, and, at least comparable to those of rEVAR. EVAR-first strategy for ruptured AAA might not be applicable to all cases. Patent-specific, individualized treatment should be the gold standard. For patients requiring rOAR, transfer to a regional center of excellence, when clinical safe, should be encouraged.
Assuntos
Aneurisma da Aorta Abdominal , Ruptura Aórtica , Implante de Prótese Vascular , Bases de Dados Factuais , Procedimentos Endovasculares , Mortalidade Hospitalar , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Humanos , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Masculino , Idoso , Ruptura Aórtica/cirurgia , Ruptura Aórtica/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Feminino , Fatores de Risco , Idoso de 80 Anos ou mais , Resultado do Tratamento , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Fatores de Tempo , Estudos Retrospectivos , Medição de Risco , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estados Unidos , Correção Endovascular de AneurismaRESUMO
BACKGROUND: Care fragmentation (CF) is a known risk factor for unplanned readmission, morbidity, and mortality after surgery. The goal of this study was to evaluate the impact of CF on outcomes of major lower extremity amputation for peripheral vascular disease. METHODS: Health-care Cost and Utilization Project Database for NY (2016) and MD/FL (2016-2017) were queried using International Classification of Diseases 10thedition to identify patients who underwent above the knee-, through the knee-, and below the knee-amputation for peripheral vascular disease. Patients with CF were identified as those with admissions to ≥2 hospitals during the study period. We compared the postamputation outcomes of mortality, readmission rate, length of stay (LOS) and hospital charges. RESULTS: We identified a total of 13,749 encounters of 2,742 patients who underwent major lower extremity amputations. There were 1,624 (59.2%) patients with CF. Patients with CF were younger (68.4 years old vs. 69.7 years old, P = 0.005), with higher Charlson Comorbidity Indices (4.4 vs. 4.1, P < 0.001), and required more hospital resources on index admission ($113,699 vs. $91,854, P < 0.001). These patients were prevalent for higher 30-, and 90-day readmission rates (34.7% vs. 24.5%, P < 0.001 and 54.7% vs. 42.0%, P < 0.001, respectively). On their first postamputation readmission, LOS (16.3 days vs. 14.7 days, P = 0.004) and hospital charge ($48,964 vs. $44,388, P = 0.002) were significantly higher. Multivariate regression analysis demonstrated that the CF was an independent predictor for 30-day (hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.39-1.96, P < 0.001) and 90-day (HR 1.66, 95% CI 1.42-1.95, P < 0.001) readmission after the major lower extremity amputation, but not for mortality (HR 0.83, 95% CI 0.56-1.23, P = 0.36). CONCLUSIONS: CF after major lower extremity amputation is associated with higher readmission rate, LOS, and hospital charge. Collaboration of care providers to maintain continuity of care for peripheral vascular disease patients may enhance quality of care and reduce health care cost.
Assuntos
Doença Arterial Periférica , Doenças Vasculares Periféricas , Humanos , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Extremidade Inferior/irrigação sanguínea , Amputação Cirúrgica/efeitos adversos , Readmissão do Paciente , Fatores de Risco , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/cirurgiaRESUMO
The study of peripheral vasculopathy with chronic metabolic disease is challenged by divergent contributions from spatial (the level of resolution or specific tissue being studied) and temporal origins (evolution of the developing impairments in time). Over many years of studying the development of skeletal muscle vasculopathy and its functional implications, we may be at the point of presenting an integrated conceptual model that addresses these challenges within the obese Zucker rat (OZR) model. At the early stages of metabolic disease, where systemic markers of elevated cardiovascular disease risk are present, the only evidence of vascular dysfunction is at postcapillary and collecting venules, where leukocyte adhesion/rolling is elevated with impaired venular endothelial function. As metabolic disease severity and duration increases, reduced microvessel density becomes evident as well as increased variability in microvascular hematocrit. Subsequently, hemodynamic impairments to distal arteriolar networks emerge, manifesting as increasing perfusion heterogeneity and impaired arteriolar reactivity. This retrograde "wave of dysfunction" continues, creating a condition wherein deficiencies to the distal arteriolar, capillary, and venular microcirculation stabilize and impairments to proximal arteriolar reactivity, wall mechanics, and perfusion distribution evolve. This proximal arteriolar dysfunction parallels increasing failure in fatigue resistance, hyperemic responses, and O2 uptake within self-perfused skeletal muscle. Taken together, these results present a conceptual model for the retrograde development of peripheral vasculopathy with chronic metabolic disease and provide insight into the timing and targeting of interventional strategies to improve health outcomes.NEW & NOTEWORTHY Working from an established database spanning multiple scales and times, we studied progression of peripheral microvascular dysfunction in chronic metabolic disease. The data implicate the postcapillary venular endothelium as the initiating site for vasculopathy. Indicators of dysfunction, spanning network structures, hemodynamics, vascular reactivity, and perfusion progress in an insidious retrograde manner to present as functional impairments to muscle blood flow and performance much later. The silent vasculopathy progression may provide insight into clinical treatment challenges.
Assuntos
Doenças Metabólicas , Síndrome Metabólica , Doenças Vasculares Periféricas , Animais , Síndrome Metabólica/metabolismo , Microcirculação/fisiologia , Músculo Esquelético/irrigação sanguínea , Obesidade/complicações , Ratos , Ratos ZuckerRESUMO
OBJECTIVE: The interfacility transfer (IT) of patients with a ruptured abdominal aortic aneurysm (rAAA) occurs not infrequently to allow for a higher level of care. In the present study, we evaluated, using a contemporary administrative database, the effects of IT on mortality after rAAA repair. METHODS: The Healthcare Cost and Utilization Project Database for New York (2016) and New Jersey, Maryland, and Florida (2016-2017) was queried using the International Classification of Diseases, 10th edition, to identify patients who had undergone open or endovascular repair of AAAs. The hospitals were categorized into quartiles (Qs) per overall volume. The mortality rates for IT vs nontransferred (NT) rAAA patients stratified by treatment modality (open aneurysm repair of an rAAA [rOAR] vs endovascular aneurysm repair of an rAAA [rEVAR]) were compared. A Cox proportional hazard model was used to estimate the hazard ratios (HRs) for mortality. RESULTS: A total of 1476 patients had presented with a rAAA, of whom 673 (45.7%) were not treated. Of the remaining 803 patients, 226 (28.1%) were transferred, of whom 50 (22.1%) had died without repair after IT. The remaining 753 patients (IT, n = 176; NT, n = 576) had undergone rEVAR (n = 492) or rOAR (n = 261). The baseline characteristics were similar between the IT and NT patients, except for a greater proportion of black patients (P = .03), lower income families (P = .049), and rOAR (45.5% vs 31.4%; P = .001) for the IT patients. The overall mortality rates were similar between the NT (30.2%) and IT (27.3%) groups (P = .46). The subgroup analysis revealed that the operative mortality rates after rEVAR were similar between the NT and IT patients, without significant differences among the hospital quartiles. After rOAR, however, the operative mortality rates were lower for the IT patients, largely owing to improved outcomes in the Q4 hospitals (Q4 vs Q1-Q3, P = .001). Cox regression analysis demonstrated that age (HR, 1.03; 95% confidence interval, 1.00-1.06; P = .02) and treatment at a low-volume hospital (Q1-Q3; HR, 1.89; 95% confidence interval, 1.02-3.51; P = .04) were predictors of mortality. The total charges were similar (IT, $286,727; vs NT, $265,717; P = .38). CONCLUSIONS: The results from the present study have shown that <30% of rAAA patients deemed a candidate for repair will be transferred. We found that IT did not affect the mortality rates after rEVAR, irrespective of the hospital volume. For rOAR candidates, however, regionalization of care with prompt transfer to a high-volume center could improve the survival benefits without increased healthcare costs.
Assuntos
Aneurisma da Aorta Abdominal , Ruptura Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Fatores de Tempo , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/cirurgia , Hospitais com Baixo Volume de Atendimentos , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Vascular abnormalities, including dissections and aneurysms, can be found in patients with autosomal dominant kidney disease (ADPKD). While intracranial aneurysms have been reported in 10%-25% of ADPCKD, occurrences at other locations are exceedingly rare. METHOD: This is a first case report of a patient with ADPCKD who presented with a rupture of the left external carotid artery pseudoaneurysm. CONCLUSION: Rupture of a carotid artery aneurysm is rare with potentially high morbidity. An endovascular and surgical approach are effective strategies for successful management that depends on etiology, location, and surgeon experience.
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Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT01331863.
Assuntos
Aorta/transplante , Bioengenharia/métodos , Brônquios/cirurgia , Neoplasias Pulmonares/cirurgia , Stents , Traqueia/cirurgia , Doenças da Traqueia/cirurgia , Adulto , Idoso , Autoenxertos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Procedimentos de Cirurgia Plástica/métodos , Traqueia/patologia , Doenças da Traqueia/patologia , Estenose Traqueal/cirurgiaRESUMO
BACKGROUND: Rates of major venous injury are now being reported at between 1% and 15%. Risk factors for injury include the previous spine surgery, level of exposure, and number of retractors used. To review and describe the evolution of our use of stent grafts for repair of life-threatening ilio-caval injuries encountered during anterior exposure lumbosacral (L-S) spine surgery from rescue utilization after failed direct repair to preferred modality using occlusion balloons and covered stents akin to the modern management of the ruptured abdominal aortic aneurysm (AAA) with endovascular aneurysm repair. METHODS: Five-year retrospective review of all anterior and retroperitoneal spine procedures was performed at our institution. RESULTS: One hundred two procedures were done. Major ilio-caval injury occurred in 3/102 (2.9%) cases. Average blood loss per case decreased as our approach evolved from unsuccessful direct open repair with percutaneous endovascular rescue to primary percutaneous endovascular repair. All treated patients had patent venous repair in short-term follow-up with computed tomography angiography. CONCLUSIONS: Identification and rapid direct repair of major ilio-caval injuries during anterior approach spine surgery can be extremely challenging. When control of these potentially fatal injuries is required, our choice is primary endovascular repair using the modern techniques for endovascular management of ruptured AAA with endovascular aneurysm repair.
Assuntos
Implante de Prótese Vascular , Procedimentos Endovasculares , Veia Ilíaca/cirurgia , Vértebras Lombares/cirurgia , Sacro/cirurgia , Fusão Vertebral/efeitos adversos , Lesões do Sistema Vascular/cirurgia , Veia Cava Inferior/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/lesões , Masculino , Pessoa de Meia-Idade , Flebografia/métodos , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/lesõesRESUMO
To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning "healthy" to "high PVD risk" and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk.
Assuntos
Microcirculação , Músculo Esquelético/irrigação sanguínea , Doenças Vasculares Periféricas/fisiopatologia , Animais , Arteríolas/fisiopatologia , Frutose/farmacologia , Hipertensão Renal/fisiopatologia , Músculo Esquelético/fisiopatologia , Óxido Nítrico/metabolismo , Consumo de Oxigênio/fisiologia , Perfusão , Ratos , Ratos Endogâmicos Dahl , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Ratos Zucker , Medição de Risco , Sódio na Dieta/farmacologia , Tromboxano A2/metabolismoRESUMO
The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16-17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS.
Assuntos
Circulação Cerebrovascular , Transtornos Cerebrovasculares/fisiopatologia , Síndrome Metabólica/fisiopatologia , Artéria Cerebral Média/fisiopatologia , Obesidade/fisiopatologia , Resistência Vascular , Fatores Etários , Animais , Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Fenômenos Biomecânicos , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/prevenção & controle , Modelos Animais de Doenças , Progressão da Doença , Relação Dose-Resposta a Droga , Mediadores da Inflamação/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/tratamento farmacológico , Artéria Cerebral Média/efeitos dos fármacos , Artéria Cerebral Média/metabolismo , Óxido Nítrico/metabolismo , Obesidade/sangue , Obesidade/tratamento farmacológico , Estresse Oxidativo , Ratos Zucker , Remodelação Vascular , Resistência Vascular/efeitos dos fármacos , Rigidez Vascular , Vasodilatação , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: Chronic presentation of the MS is associated with an increased likelihood for stroke and poor stroke outcomes following occlusive cerebrovascular events. However, the physiological mechanisms contributing to compromised outcomes remain unclear, and the degree of cerebral cortical MVD may represent a central determinant of stroke outcomes. METHODS: This study used the OZR model of MS and clinically relevant, chronic interventions to determine the impact on cerebral cortical microvascular rarefaction via immunohistochemistry with a parallel determination of cerebrovascular function to identify putative mechanistic contributors. RESULTS: OZR exhibited a progressive rarefaction (to ~80% control MVD) of the cortical microvascular networks vs. lean Zucker rats. Chronic treatment with antihypertensive agents (captopril/hydralazine) had limited effectiveness in blunting rarefaction, although treatments improving glycemic control (metformin/rosiglitazone) were superior, maintaining ~94% control MVD. Chronic treatment with the antioxidant TEMPOL severely blunted rarefaction in OZR, although this ameliorative effect was prevented by concurrent NOS inhibition. CONCLUSIONS: Further analyses revealed that the maintenance of glycemic control and vascular NO bioavailability were stronger predictors of cerebral cortical MVD in OZR than was prevention of hypertension, and this may have implications for chronic treatment of CVD risk under stroke-prone conditions.
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Córtex Cerebral , Circulação Cerebrovascular , Resistência à Insulina , Síndrome Metabólica , Microcirculação , Óxido Nítrico/metabolismo , Animais , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Ratos , Ratos Zucker , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Depression is recognized as a predictor of increased cardiac morbidity and mortality. In addition, depressed patients exhibit an increase in the serum markers of endothelial dysfunction and platelet activation involved in the cascade of events leading to atherosclerosis. The purpose of this study was to determine the early and late-onset expression of various vascular markers in a rodent model of depression. Male DBA (an inbred strain of mice)/2J mice were exposed to either 7 weeks of controlled living conditions or unpredictable chronic mild stress (UCMS), and subsequently given daily fluoxetine (10 mg/kg) or NaCl (9%) during the last 5 weeks of the experiment. Depressive-like behavior was evaluated by using motivational and self-care behavior, including the assessment of the animal's coat state and grooming behavior. Enzyme-linked immunoassay was used to quantify matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1) expression either immediately after the end of the UCMS procedure (short term condition) or 10 months later (long-term condition). Results indicate that 1) UCMS procedure induces a short-term depressive-like behavior in mice, defined as coat state deterioration, an effect that is prevented by fluoxetine treatment; 2) UCMS procedure has no effect on the short-term expression of the studied markers; however, UCMS increases expression of plasminogen activator inhibitor-1 only in the long-term group; 3) fluoxetine treatment is unable to counteract this UCMS-induced change; 4) aging induces behavioral perturbation, defined as a decrease in grooming motivation, and an increase of all the vascular markers in both control and UCMS groups and 5) pretreatment with fluoxetine has no protective effects on aging-induced behavioral and vascular alterations. Thus, in this model of depression-like behavior, UCMS appears to induce late-onset physiological changes, which are consistent with human studies indicating that depression is a risk factor for the development of heart disease.
Assuntos
Envelhecimento/fisiologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Modelos Animais de Doenças , Fluoxetina/uso terapêutico , Inibidor 1 de Ativador de Plasminogênio/sangue , Estresse Psicológico/fisiopatologia , Doenças Vasculares/fisiopatologia , Envelhecimento/sangue , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Depressão/sangue , Depressão/complicações , Fluoxetina/farmacologia , Asseio Animal/efeitos dos fármacos , Asseio Animal/fisiologia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Camundongos , Camundongos Endogâmicos DBA , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Estresse Psicológico/sangue , Estresse Psicológico/complicações , Molécula 1 de Adesão de Célula Vascular/sangue , Doenças Vasculares/sangue , Doenças Vasculares/complicaçõesRESUMO
One clinical intervention against the negative outcomes associated with atherothrombotic vascular disease (AVD) is low-dose, chronic aspirin therapy. However, epidemiological studies suggest that recurrence of adverse vascular events with aspirin therapy is growing and associated with therapy duration. The contributors to this outcome are unclear and include poor patient compliance and aspirin-resistant platelet thromboxane A(2) (TxA(2)) production. Based on previous results in hypercholesterolemic mice, we hypothesized that elevated aspirin-insensitive arachidonic acid (AA)-induced TxA(2) production by the vascular endothelium contributes to aspirin resistance in AVD independent of platelet behavior. AA-induced dilation was blunted in aortic rings and in arterioles from apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) gene deletion mice (vs. C57/Bl6/J), partially due to elevated TxA(2) production. Acute inhibition of cyclooxygenases or TxA(2) synthase attenuated the increased TxA(2) production in ApoE and LDLR and improved AA-induced dilation, responses that were mirrored by chronic treatment with low-dose aspirin of 16 wk duration. However, this effect was not temporally stable, and, with longer-duration therapy, the beneficial impact of aspirin on outcomes diminished. A similar, though less robust, pattern to the impact of chronic aspirin therapy on vascular outcomes was identified with chronic antioxidant treatment (TEMPOL). These results suggest that in dyslipidemic mice, the beneficial impact of chronic aspirin therapy on improving vascular outcomes decay with time and that a contributing element to subsequent negative vascular events may be the development of aspirin-resistant TxA(2) production by the vasculature itself.
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Aspirina/uso terapêutico , Vasos Sanguíneos/metabolismo , Resistência a Medicamentos , Dislipidemias/genética , Dislipidemias/metabolismo , Tromboxano A2/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/genética , Arteríolas/efeitos dos fármacos , Resistência a Medicamentos/genética , Dislipidemias/complicações , Dislipidemias/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de LDL/genéticaRESUMO
Genetic familial hypercholesterolemia (FH) and combined hyperlipidemia (FCH) are characterized by elevated plasma low-density lipoprotein (LDL) (FH) and LDL/triglycerides (FCH), with mouse models represented by LDL receptor (LDLR) and apolipoprotein E (ApoE) gene deletion mice, respectively. Given the impact of FH and FCH on health outcomes, we determined the impact of FH/FCH on vascular structure in LDLR and ApoE mice. LDLR, ApoE and control mice were utilized at 12-13 and 22-23 weeks when gracilis arteries were studied for wall mechanics and gastrocnemius muscles were harvested for microvessel density measurements. Conduit arteries and plasma samples were harvested for biochemical analyses. Arteries from ApoE and LDLR exhibited blunted expansion versus control, reduced distensibility and left-shifted stress versus strain relation (LDLR > ApoE). Microvessel density was reduced in ApoE and LDLR (ApoE > LDLR). Secondary analyses suggested that wall remodeling in LDLR was associated with cholesterol and MCP-1, while rarefaction in ApoE was associated with tumor necrosis factors-alpha, triglycerides and vascular production of TxA(2). Remodeling in ApoE and LDLR appears distinct; as that in LDLR is preferential for vascular walls, while that for ApoE is stronger for rarefaction. Remodeling in LDLR may be associated with cellular adhesion, while that in ApoE may be associated with pro-apoptotsis and constrictor prostanoid generation.
Assuntos
Hiperlipidemia Familiar Combinada/patologia , Hiperlipoproteinemia Tipo II/patologia , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Ácido Araquidônico/metabolismo , Arteríolas/patologia , Arteríolas/fisiopatologia , Modelos Animais de Doenças , Hiperlipidemia Familiar Combinada/genética , Hiperlipidemia Familiar Combinada/fisiopatologia , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microcirculação/fisiologia , Músculo Esquelético/irrigação sanguínea , Óxido Nítrico/metabolismo , Receptores de LDL/deficiência , Receptores de LDL/genéticaRESUMO
OBJECTIVE: Surgical revascularization is the standard treatment of complex blunt traumatic extremity vascular injuries. Limb salvage may be improved with minimally invasive endovascular therapies because of the ability to perform diagnostic and therapeutic intervention simultaneously. Two cases of acute limb-threatening arterial injuries successfully treated with percutaneous endovascular therapy are reported. RESULTS: A skier suffered hemodynamic instability after shoulder reduction. An axillary arterial injury was suspected and confirmed with angiography. A covered stent successfully controlled the hemorrhage. A morbidly obese female sustained anterior dislocation of her left knee 7 years previously requiring repair. She developed recurrent knee dislocation with acute leg ischemia. Emergent fixation was performed followed by percutaneous angiography. Short segment thrombosis of the popliteal was noted. Wire recanalization of the thrombosed artery and stent placement restored 3-vessel runoff. CONCLUSION: Endovascular therapy can offer faster, easier access to the extremity vascular injury facilitating revascularization and avoiding long incisions and dissections.
Assuntos
Angioplastia com Balão , Arteriopatias Oclusivas/terapia , Extremidades/irrigação sanguínea , Hemorragia/terapia , Técnicas Hemostáticas , Manipulação Ortopédica/efeitos adversos , Procedimentos Ortopédicos/efeitos adversos , Trombose/terapia , Ferimentos não Penetrantes/terapia , Adulto , Angioplastia com Balão/instrumentação , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/etiologia , Artérias/lesões , Feminino , Hematoma/etiologia , Hematoma/terapia , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Técnicas Hemostáticas/instrumentação , Humanos , Luxação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia , Luxação do Ombro/terapia , Esqui , Stents , Trombose/diagnóstico por imagem , Trombose/etiologia , Resultado do Tratamento , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/etiologiaRESUMO
OBJECTIVE: The aim of this study was to determine if arachidonic acid (AA)-induced skeletal muscle arteriolar dilation is altered with hypercholesterolemia in ApoE and low-density lipoprotein receptor (LDLR) gene deletion mice fed a normal diet. This study also determined contributors to altered AA-induced dilation between dyslipidemic mice and controls, C57/Bl/6J (C57). METHODS: Gracilis muscle arterioles were isolated, with mechanical responses assessed following a challenge with AA under control conditions and after elements of AA metabolism pathways were inhibited. Conduit arteries from each strain were used to assess AA-induced production of PGI(2) and TxA(2). RESULTS: Arterioles from ApoE and LDLR exhibited a blunted dilation to AA versus C57. While responses were cyclo-oxygenase-dependent in all strains, inhibition of thromboxane synthase or blockade of PGH(2)/TxA(2) receptors improved dilation in ApoE and LDLR only. AA-induced generation of PGI(2) was comparable across strains, although TxA(2) generation was increased in ApoE and LDLR. Arteriolar reactivity to PGI(2) and TxA(2) was comparable across strains. Treatment with TEMPOL improved dilation and reduced TxA(2) production with AA in ApoE and LDLR. CONCLUSIONS: These results suggest that AA-induced arteriolar dilation is constrained in ApoE and LDLR via an increased production of TxA(2). While partially due to elevated oxidant stress, additional mechanisms contribute that are independent of acute alterations in oxidant tone.
Assuntos
Ácido Araquidônico/metabolismo , Hipercolesterolemia/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Vasodilatação/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Arteríolas/metabolismo , Óxidos N-Cíclicos/farmacologia , Técnicas de Silenciamento de Genes , Hipercolesterolemia/genética , Hipercolesterolemia/fisiopatologia , Camundongos , Camundongos Mutantes , Prostaglandina H2/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Marcadores de Spin , Tromboxano A2/metabolismoRESUMO
We describe the inadvertent cannulation of the proximal descending thoracic aortic stent with a five French sheath during attempted pacemaker placement in an 88- year-old male. The injury was managed successfully by the percutaneous placement of a thoracic aortic stent graft with good outcome. Our case highlights the feasibility of managing this uncommon injury with this technique.
RESUMO
This report presents an unusual case of traumatic iliofemoral vessel transection in a 3-year-old patient successfully reconstructed using a cryopreserved greater saphenous conduit. Five years after injury, the patient continues to do well with normal ambulation. An arterial duplex demonstrated graft patency free of aneurysmal dilatation. These encouraging results suggest that the natural history of cryopreserved conduits may differ in the pediatric population and cryopreserved conduits could be used for complex vascular reconstructions.
Assuntos
Mordeduras e Picadas/cirurgia , Criopreservação , Artéria Femoral/cirurgia , Veia Femoral/cirurgia , Procedimentos de Cirurgia Plástica , Veia Safena/transplante , Enxerto Vascular/métodos , Lesões do Sistema Vascular/cirurgia , Animais , Mordeduras e Picadas/diagnóstico por imagem , Mordeduras e Picadas/fisiopatologia , Pré-Escolar , Cães , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/lesões , Artéria Femoral/fisiopatologia , Veia Femoral/diagnóstico por imagem , Veia Femoral/lesões , Veia Femoral/fisiopatologia , Humanos , Masculino , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/fisiopatologiaRESUMO
Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression have been reported, the unpredictable chronic mild stress (UCMS) protocol is an established translationally-relevant model for inducing behavioral symptoms commonly associated with clinical depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS protocol also induces physiological (e.g., hypercortisolemia, hypertension) and neurological (e.g., anhedonia, learned helplessness) changes that are clinically associated with depression. Importantly, UCMS-induced depressive symptoms can be ameliorated through chronic, but not acute, treatment with common SSRIs. As such, the UCMS protocol offers many advantages over acute stress protocols or protocols that utilize more extreme stressors. Our protocol involves randomized, daily exposures to 7 distinct stressors: damp bedding, removal of bedding, cage tilt, alteration of light/dark cycles, social stresses, shallow water bath, and predator sounds/smells. By subjecting rodents 3-4 hr daily to these mild stressors for 8 weeks, we demonstrate both significant behavioral changes and poor health outcomes to the cardiovascular system. This approach allows for in-depth interrogation of the neurological, behavioral, and physiological alterations associated with chronic stress-induced depression, as well as for testing of new potential therapeutic agents or intervention strategies.
RESUMO
BACKGROUND: The management of non-small cell carcinomas of the lung involving the superior sulcus remains controversial. The goal of this retrospective study was to evaluate the role of surgery, radiotherapy, and chemotherapy for the treatment of superior sulcus tumors, to define the best surgical approach for radical resection, and to identify factors influencing long-term survival. METHODS: Between 1983 and 1999, 139 patients underwent surgical resection of superior sulcus tumors in seven thoracic surgery centers. According to the classification of the American Joint Committee, 51.1% of cancers were stage IIB, 13.7% stage IIIA, 32.4% stage IIIB, and 2.9% stage IV. RESULTS: The resections were performed with 74.1% using the posterior approach and 25.9% using an anterior approach. A lobectomy was accomplished in 69.8% of the cases and a wedge resection in 22.3%. Resection of a segment of vertebrae or subclavian artery was performed, respectively, in 19.4% and 18% of the cases. Resection was complete in 81.3% of cancers. The overall 5-year survival rate was 35%. Preoperative radiotherapy improved 5-year survival for stages IIB-IIIA. Surgical approach, postoperative radiotherapy, or chemotherapy did not change survival. CONCLUSIONS: The optimal treatment for superior sulcus tumors is complete surgical resection. The surgical approach (anterior/posterior) did not influence the 5-year survival rate. Preoperative radiotherapy should be recommended to improve outcome of patients with a superior sulcus tumor.