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1.
Cardiol Young ; 33(4): 514-519, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37132393

RESUMO

PURPOSE: Diversification of the medical and cardiothoracic surgical workforce represents an ongoing need. A congenital cardiac surgery shadowing programme for undergraduate students was implemented at the University of Florida Congenital Heart Center. METHODS: Students shadowing in the Congenital Heart Center from 17 December 2020 through 20 July 2021 were sent a survey through Qualtrics to evaluate the impact of their shadowing experience. The main objectives of the survey were to determine the personal relationship(s) of the students to physicians prior to shadowing, how the presence or absence of physicians in the family of a given student related to the exposure of the student to a medical setting prior to shadowing, and the interest of the students in medicine and cardiothoracic surgery prior to and after the shadowing experience. Survey responses included "Yes/No" questions, scaled responses using a Likert scale, selection lists, and free text responses. When applicable, t-tests were utilised to assess differences between student groups. RESULTS: Of the 37 students who shadowed during the study period, 26 (70%) responded. Most students were female (58%, n = 15), and the mean age was 20.9 ± 2.4 years. Students spent a mean duration of 95 ± 138 hours shadowing providers as part of the shadowing programme. Likert scale ratings of interest in the professions of medicine, surgery, and cardiothoracic surgery all increased after the shadowing experience (p < 0.01). Students with a family member in medicine had more clinical exposure prior to the shadowing programme (p < 0.01). CONCLUSION: A surgical shadowing programme at a Congenital Heart Center may have an important formative impact on the views of undergraduate students regarding potential careers in surgery and medicine. Additionally, students without family members in medicine tend to have less prior exposure to medicine and could likely benefit more from this type of shadowing programme.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Especialidades Cirúrgicas , Cirurgia Torácica , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Masculino , Escolha da Profissão , Estudantes
3.
Ann Thorac Surg ; 115(2): e53-e55, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35288081

RESUMO

A large patent ductus arteriosus is an uncommon discovery in an adult. A 2.7-cm patent ductus arteriosus was found in a 31-year-old man with heart failure symptoms. Owing to the size, an occluder device failed to prevent left-to-right shunting, and consideration was given for alternatives to percutaneous closure, including traditional open repair vs thoracic endovascular aortic repair (TEVAR). After a left carotid-subclavian artery bypass was performed, the patient underwent a zone 2 deployment of TEVAR graft. TEVAR exclusion is a useful technique in adults, particularly in the setting of a large or calcified ductus.


Assuntos
Permeabilidade do Canal Arterial , Procedimentos Endovasculares , Insuficiência Cardíaca , Masculino , Adulto , Humanos , Permeabilidade do Canal Arterial/cirurgia , Permeabilidade do Canal Arterial/diagnóstico , Correção Endovascular de Aneurisma , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Procedimentos Endovasculares/métodos , Insuficiência Cardíaca/cirurgia , Resultado do Tratamento
4.
Innovations (Phila) ; 17(6): 482-490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317252

RESUMO

OBJECTIVE: Surgical aortic valve replacement (SAVR) has been the standard of care for severe aortic stenosis. In 2019, annual transcatheter aortic valve replacement (TAVR) implantations surpassed SAVR. We compared in-hospital costs and outcomes between these two procedures. METHODS: A single-center retrospective review was performed of patients who underwent isolated SAVR or TAVR from October 2013 to December 2019. Baseline patient characteristics, operating room (OR) time, intensive care unit (ICU) length of stay (LOS), total LOS, cumulative cost, and complication rates were collected. Propensity matching was performed to identify differences in costs and outcomes between comparable groups. RESULTS: There were 515 patients who met inclusion criteria. TAVR was performed in 402 patients, while SAVR was performed in 113. Propensity matching resulted in 82 matched pairs. The SAVR cohort more frequently spent >1 day in the ICU, had longer total hospital LOS, longer OR time, and higher hospitalization cost. However, TAVR was associated with higher mean OR cost and higher valve cost. The cumulative index admission costs were not significantly different between groups. TAVR patients had less postoperative atrial fibrillation but more frequent pacemaker placement. One-year mortality was similar between SAVR (2.4%) and TAVR (3.8%), but 3-year (5.8% vs 19.2%) and 5-year (5.8% vs 37.2%) mortality favored SAVR. CONCLUSIONS: In propensity-matched groups, TAVR was associated with shorter ICU and hospital LOS and OR times but increased permanent pacemaker rates. In addition, while 1-year survival was similar between groups, SAVR had significantly improved 3-year and 5-year survival.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Implante de Prótese de Valva Cardíaca/métodos , Estenose da Valva Aórtica/complicações , Resultado do Tratamento , Valva Aórtica/cirurgia , Custos Hospitalares , Fatores de Risco
5.
Innovations (Phila) ; 17(5): 401-408, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36217748

RESUMO

OBJECTIVE: Monitored anesthesia care (MAC) has been increasingly used in lieu of general anesthesia (GA) for transcatheter aortic valve replacement (TAVR). We sought to compare outcomes and in-hospital costs between MAC and GA for TAVR at a Veterans Affairs Medical Center. METHODS: A single-center retrospective review was performed of 349 patients who underwent transfemoral TAVR (MAC, n = 244 vs GA, n = 105) from January 2014 to December 2019. Baseline patient characteristics, operating room (OR) time, intensive care unit (ICU) length of stay (LOS), and cost, total LOS, hospital cost, total cost, and complication rates were collected. Propensity matching was performed and resulted in 83 matched pairs. RESULTS: In the unmatched TAVR cohort, MAC TAVR was associated with reduced OR time (146 vs 198 min, P < 0.001), ICU LOS (1.4 vs 1.8 days, P < 0.001), total hospital LOS (3.4 vs 5.4 days, P < 0.001), and lower index total cost ($81,300 vs $85,400, P = 0.010). After propensity matching, MAC TAVR patients had reduced OR time (146 vs 196 min, P < 0.05), ICU LOS (1.2 vs 1.7 days, P = 0.006), total LOS (3.5 vs 5.1 days, P = 0.001), and 180-day mortality (2.4% vs 12%, P < 0.03). There was no difference in total hospitalization cost or total cost. CONCLUSIONS: In propensity-matched groups, TAVR utilizing MAC is associated with improved OR time efficiency, decreased LOS, and a reduction in 180-day mortality but no significant difference in cost.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento , Anestesia Geral/métodos , Tempo de Internação , Estudos Retrospectivos , Fatores de Risco , Valva Aórtica/cirurgia
7.
Ann Thorac Surg ; 113(2): 663-668, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33774001

RESUMO

BACKGROUND: The 2020 interview cycle for cardiothoracic fellowships was affected by the coronavirus-19 pandemic. Many programs shifted from in-person to virtual interviews. We evaluated applicant perceptions of the various formats. METHODS: All 2019-2020 cardiothoracic fellowship applicants received an electronic survey after completion of the match process. The survey assessed number of in-person/virtual interviews completed, perception of efficacy, and likelihood of ranking a program based on format, and strengths/inadequacies of virtual interviews. RESULTS: Response rate was 36% (48 of 133). Seventy-three percent of respondents (35 of 48) interviewed with more than 10 programs. Fifty-two percent of respondents (25 of 48) were able to schedule additional interviews once virtual formats were available. A slight majority (56%, 27 of 48) ranked a program at which they had an in-person interview as their first choice. Interviewing at more than 10 programs was associated with an increased likelihood of successfully matching at a program (P = .02). Overwhelmingly, respondents favored an in-person component to the interview process (96%, 46 of 48). Few respondents (29%, 14 of 48) thought they could adequately evaluate a program virtually. The factors that had the highest percentages of adequate portrayal during virtual interviews were the didactic schedule/curriculum (81%, 39 of 48) and case number/autonomy (58%, 28 of 48). The factors with the lowest percentages were culture/personality (19%, 9 of 48) and city/lifestyle (15%, 7 of 48). CONCLUSIONS: Applicants strongly favored an in-person component to interviews, highlighting potential deficiencies in the virtual interview process. Programs should consider the addition of virtual tours of their hospitals, narrations from staff, and vignettes from current fellows about lifestyle and well-being.


Assuntos
COVID-19/epidemiologia , Internato e Residência , Entrevistas como Assunto , SARS-CoV-2 , Cirurgia Torácica/educação , Bolsas de Estudo , Humanos
8.
J Thorac Cardiovasc Surg ; 164(6): e475-e482, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34955283

RESUMO

OBJECTIVES: Cardiothoracic programs used virtual interviews exclusively this year. As programs consider using virtual interviews permanently, our goal was to evaluate the experience of applicants with virtual interviews. METHODS: All 2020-2021 traditional cardiothoracic fellowship applicants received an anonymous electronic survey after the Match process ended. The survey assessed the number of interviews, strengths, and inadequacies of virtual interviews and factors that affected rank decision. RESULTS: Forty-three percent of applicants responded (60/139). The average number of interviews was 16.0. Eighty percent (48/60) of respondents successfully matched. Eighty-seven percent (52/60) of respondents had a favorable experience with virtual interviews, and 97% (58/60) found them to be convenient. However, only 50% (30/60) were able to evaluate a program fully. Respondents who matched were more likely to have a favorable experience (P = .02), but not more likely to be able to evaluate a program fully (P = .35). The most valued aspect was the informal meet and greet session with fellows (4.2 of 5). The least valued aspect was the program's social media site (2.0 of 5). The factors most frequently used to decide ranking were case numbers by 92% (55/60) and culture/personality by 82% (49/60). CONCLUSIONS: Virtual interviews were perceived more favorably compared with last year, but half of applicants were still unable to evaluate a program fully. Fellow interactions were the most popular aspect of virtual interviews. As programs consider using virtual interviews permanently, more exposure to current trainees and a more robust social media/online presence will improve favorability.


Assuntos
Bolsas de Estudo , Entrevistas como Assunto , Cirurgia Torácica , Humanos , Percepção , Inquéritos e Questionários , Cirurgia Torácica/educação , Entrevistas como Assunto/métodos , Comunicação por Videoconferência
9.
Ann Thorac Surg ; 114(6): 2202-2208, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34838743

RESUMO

BACKGROUND: Acute aortic syndromes (AASs) are prone to misdiagnosis by facilities with limited diagnostic experience. We assessed long-term trends in misdiagnosis among patients transferred to a tertiary care facility with presumed AASs. METHODS: Our institutional transfer center database was queried for emergency transfers in patients with a diagnosis of AASs or thoracic aortic aneurysm between January 2008 and May 2018. There were 784 patients classified as emergency transfer for presumed AAS. Transferring diagnosis and actual diagnosis were compared through a review of physician notes and radiology reports from referring facilities and our center. RESULTS: Mean age was 62 years, with 478 (61%) men. Differences in transferring diagnosis and actual diagnosis were identified in 89 patients (11.4%). Among misdiagnosed patients, the wrong classification of Stanford type A or type B dissections was identified among 24 patients (27%). No dissection was found in 23 patients (26%) with a referring diagnosis of aortic dissection. No signs of rupture were found in 18 patients (20%) transferred for contained/impending rupture. All misdiagnoses were secondary to misinterpretation of radiographic imaging, with motion artifacts in 14 (16%) and postsurgical changes in 22 (25%) being common sources of diagnostic error. Repeat scans were performed in 64 patients (72%) at our facility due to limited access to or suboptimal quality of outside imaging. CONCLUSIONS: Although AASs misdiagnosis rates appear to be improving from the prior decade, there are opportunities for improved physician awareness through campaigns such as "Think Aorta." Centralized web-based imaging may prevent the costly hazards of unnecessary emergency transfer.


Assuntos
Aneurisma da Aorta Torácica , Doenças da Aorta , Dissecção Aórtica , Ruptura Aórtica , Doenças Torácicas , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Aorta , Erros de Diagnóstico , Doença Aguda
10.
Ann Thorac Surg ; 100(1): 41-6; discussion 46, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25865765

RESUMO

BACKGROUND: Paraplegia remains a devastating complication of aortic surgery, occurring in up to 20% of complex thoracoabdominal repairs. Erythropoietin (EPO) attenuates this injury in models of spinal cord ischemia. Upregulation of the beta-common receptor (ßcR) subunit of the EPO receptor is associated with reduced damage in murine models of neural injury. This receptor activates anti-apoptotic pathways including signaling transducer and activator of transcription 3 (STAT3). We hypothesized that spinal cord ischemia-reperfusion injury upregulates the ßcR subunit with a subsequent increase in activated STAT3. METHODS: Adult male C57/BL6 mice received an intraperitoneal injection of 0.5 mL of EPO (10 U/kg) or 0.9% saline after induction of anesthesia. Spinal cord ischemia was induced through sternotomy and 4-minute thoracic aortic cross-clamp. Sham mice underwent sternotomy without cross-clamp placement. Four groups were studied: ischemic and sham groups, each with and without EPO treatment. After 4 hours of reperfusion, spinal cords were harvested and homogenized. The ßcR subunit expression and STAT3 activation were evaluated by immunoblot. RESULTS: Ischemia reperfusion increased ßcR subunit expression in spinal cords of ischemia + saline and ischemia + EPO mice compared with shams (3.4 ± 1.39 vs 1.31 ± 0.3, p = 0.01 and 3.80 ± 0.58 vs 1.56 ± 0.32, p = 0.01). Additionally, both ischemic groups demonstrated increased STAT3 activation compared with shams (1.35 ± 0.14 vs 1.09 ± 0.07, p = 0.01 and 1.66 ± 0.35 vs 1.08 ± 0.17, p = 0.02). CONCLUSIONS: Ischemia-reperfusion injury induces EPO receptor ßcR subunit expression and early downstream anti-apoptotic signaling through STAT3 activation. Further investigation into the role of the ßcR subunit is warranted to determine tissue protective functions of EPO. Elucidation of mechanisms involved in spinal cord protection is essential for reducing delayed paraplegia.


Assuntos
Receptores da Eritropoetina/biossíntese , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/metabolismo , Medula Espinal/irrigação sanguínea , Regulação para Cima , Animais , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/fisiologia
11.
J Surg Res ; 195(1): 21-8, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25655994

RESUMO

BACKGROUND: Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. MATERIALS AND METHODS: Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 µM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. RESULTS: Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P < 0.05). Dex significantly decreased apoptotic cells compared with that of vehicle control cells by 50% (P < 0.05). Necrosis was not significantly different between treatment groups. Mechanistically, Dex treatment significantly increased phosphorylated Akt (P < 0.05), but protective effects of Dex were eliminated by an alpha-2a antagonist or Akt inhibitor (P < 0.05). CONCLUSIONS: Using a novel spinal cord neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Dexmedetomidina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Traumatismos da Medula Espinal/prevenção & controle , Animais , Apoptose , Sobrevivência Celular , Células Cultivadas , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Glucose/deficiência , Hipóxia , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Medula Espinal/citologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/etiologia
12.
J Thorac Cardiovasc Surg ; 149(3): 920-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25500291

RESUMO

OBJECTIVE: Paraplegia remains a devastating complication of complex aortic surgery. Erythropoietin (EPO) has been shown to prevent paraplegia after ischemia reperfusion, but the protective mechanism remains poorly described in the spinal cord. We hypothesized that EPO induces the CREB (cAMP [adenosine 3'5' cyclic monophosphate] response element-binding protein) pathway and neurotrophin production in the murine spinal cord, attenuating functional and cellular injury. METHODS: Adult male mice were subjected to 4 minutes of spinal cord ischemia via an aortic and left subclavian cross-clamp. Experimental groups included EPO treatment 4 hours before incision (n = 7), ischemic control (n = 7), and shams (n = 4). Hind-limb function was assessed using the Basso motor score for 48 hours after reperfusion. Spinal cords were harvested and analyzed for neuronal viability using histology and staining with a fluorescein derivative. Expression of phosphorylated (p)AKT (a serine/threonine-specific kinase), pCREB, B-cell lymphoma 2, and brain-derived neurotrophic factor were determined using immunoblotting. RESULTS: By 36 hours of reperfusion, EPO significantly preserved hind-limb function after ischemia-reperfusion injury (P < .01). Histology demonstrated preserved cytoarchitecture in the EPO treatment group. Cords treated with EPO expressed significant increases in pAKT (P = .021) and pCREB (P = .038). Treatment with EPO induced expression of both of the neurotrophins, B-cell lymphoma 2, and brain-derived neurotrophic factor, beginning at 12 hours. CONCLUSIONS: Erythropoietin-mediated induction of the CREB pathway and production of neurotrophins is associated with improved neurologic function and increased neuronal viability following spinal cord ischemia reperfusion. Further elucidation of EPO-derived neuroprotection will allow for expansion of adjunct mechanisms for spinal cord protection in high-risk thoracoabdominal aortic intervention.


Assuntos
Proteína de Ligação a CREB/metabolismo , Eritropoetina/farmacologia , Paraplegia/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Isquemia do Cordão Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Paraplegia/enzimologia , Paraplegia/fisiopatologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/fisiopatologia , Medula Espinal/enzimologia , Medula Espinal/fisiopatologia , Isquemia do Cordão Espinal/enzimologia , Isquemia do Cordão Espinal/fisiopatologia , Fatores de Tempo
13.
J Thorac Cardiovasc Surg ; 149(2): 578-84; discussion 584-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25454921

RESUMO

OBJECTIVES: Delayed paraplegia secondary to ischemia-reperfusion injury is a devastating complication of thoracoabdominal aortic surgery. Alpha-2 agonists have been shown to attenuate ischemia-reperfusion injury, but the mechanism for protection has yet to be elucidated. A growing body of evidence suggests that astrocytes play a critical role in neuroprotection by release of neurotrophins. We hypothesize that alpha-2 agonism with dexmedetomidine increases glial cell-line-derived neurotrophic factor in spinal cord astrocytes to provide spinal cord protection. METHODS: Spinal cords were isolated en bloc from C57BL/6 mice, and primary spinal cord astrocytes and neurons were selected for and grown separately in culture. Astrocytes were treated with dexmedetomidine, and glial cell-line-derived neurotrophic factor was tested for by enzyme-linked immunosorbent assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess neuronal viability. RESULTS: Spinal cord primary astrocytes treated with dexmedetomidine at 1 µmol/L and 10 µmol/L had significantly increased glial cell-line-derived neurotrophic factor production compared with control (P < .05). Neurons subjected to oxygen glucose deprivation had significant preservation (P < .05) of viability with use of dexmedetomidine-treated astrocyte media. Glial cell-line-derived neurotrophic factor neutralizing antibody eliminated the protective effects of the dexmedetomidine-treated astrocyte media (P < .05). CONCLUSIONS: Astrocytes have been shown to preserve neuronal viability via release of neurotrophic factors. Dexmedetomidine increases glial cell-derived neurotrophic factor from spinal cord astrocytes via the alpha-2 receptor. Treatment with alpha-2 agonist dexmedetomidine may be a clinical tool for use in spinal cord protection in aortic surgery.


Assuntos
Astrócitos/efeitos dos fármacos , Traumatismo por Reperfusão/complicações , Isquemia do Cordão Espinal/etiologia , Isquemia do Cordão Espinal/prevenção & controle , Medula Espinal/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Dexmedetomidina/farmacologia , Ensaio de Imunoadsorção Enzimática , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Medula Espinal/citologia
14.
J Vis Exp ; (85)2014 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-24637534

RESUMO

BACKGROUND: Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. METHODS: Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery. Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. RESULTS: Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. CONCLUSION: Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.


Assuntos
Aorta Torácica/fisiopatologia , Arteriopatias Oclusivas/etiologia , Modelos Animais de Doenças , Paraplegia/etiologia , Traumatismo por Reperfusão/etiologia , Isquemia do Cordão Espinal/etiologia , Animais , Masculino , Camundongos
15.
J Vasc Surg ; 59(4): 1090-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23850057

RESUMO

BACKGROUND: Despite investigation into preventable pharmacologic adjuncts, paraplegia continues to complicate thoracoabdominal aortic interventions. The alpha 2a adrenergic receptor agonist, dexmedetomidine, has been shown to preserve neurologic function and neuronal viability in a murine model of spinal cord ischemia reperfusion, although the mechanism remains elusive. We hypothesize that dexmedetomidine will blunt postischemic inflammation in vivo following thoracic aortic occlusion with in vitro demonstration of microglial inhibition following lipopolysaccharide (LPS) stimulation. METHODS: Adult male C57BL/6 mice underwent 4 minutes of aortic occlusion. Mice received 25 µg/kg intraperitoneal dexmedetomidine (n = 8) or 0.9% normal saline (n = 7) at reperfusion and 12-hour intervals postoperatively until 48 hours. Additionally, sham mice (n = 3), which had aortic arch exposed with no occlusion, were included for comparison. Functional scoring was done at 6 hours following surgery and 12-hour intervals until 60 hours when spinal cords were removed and examined for neuronal viability and cytokine production. Additional analysis of microglia activation was done in 12 hours following surgery. Age- and sex-matched mice had spinal cord removed for microglial isolation culture. Cells were grown to confluence and stimulated with toll-like receptor-4 agonist LPS 100 ng/mL in presence of dexmedetomidine or vehicle control for 24 hours. Microglia and media were then removed for analysis of protein expression. RESULTS: Dexmedetomidine treatment at reperfusion significantly preserved neurologic function with mice in treatment group having a Basso Score of 6.3 in comparison to 2.3 in ischemic control group. Treatment was associated with a significant reduction in microglia activation and in interleukin-6 production. Microglial cells in isolation when stimulated with LPS had an increased production of proinflammatory cytokines and markers of activation. Treatment with dexmedetomidine significantly attenuated microglial activation and proinflammatory cytokine production in vitro with a greater than twofold reduction in tumor necrosis factor-α. CONCLUSIONS: Alpha 2a agonist, dexmedetomidine treatment at reperfusion preserved neurologic function and neuronal viability. Furthermore, dexmedetomidine treatment resulted in an attenuation of microglial activation and proinflammatory cytokine production both in vivo and in vitro following LPS stimulation. This finding lends insight into the mechanism of paralysis following thoracic aortic interventions and may guide future pharmacologic targets for attenuating spinal cord ischemia and reperfusion.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Paraplegia/tratamento farmacológico , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Aorta Torácica/cirurgia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Ligadura , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Paraplegia/metabolismo , Paraplegia/fisiopatologia , Receptores Adrenérgicos alfa 2/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Fatores de Tempo , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/metabolismo
16.
Circulation ; 128(11 Suppl 1): S152-6, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24030400

RESUMO

BACKGROUND: Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia-reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in stroke models. We hypothesize that spinal cord ischemia-reperfusion injury after aortic occlusion results from TLR-4-mediated microglial activation in mice. METHODS AND RESULTS: TLR-4 mutant and wild-type mice underwent aortic occlusion for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed for analysis. Spinal cord cytokine production and microglial activation were assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild-type mice were subjected to oxygen and glucose deprivation for 24 hours, after which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice without functional TLR-4 demonstrated decreased microglial activation and cytokine production and had preserved functional outcomes and neuronal viability after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type microglia had increased TLR-4 expression and production of proinflammatory cytokines. CONCLUSIONS: The absence of functional TLR-4 attenuated neuronal injury and microglial activation after thoracic aortic occlusion in mice. Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose deprivation, and the absence of functional TLR-4 significantly attenuated the production of proinflammatory cytokines. In conclusion, TLR-4-mediated microglia activation in the spinal cord after aortic occlusion is critical in the mechanism of paraplegia after aortic cross-clamping and may provide targets for pharmacological intervention.


Assuntos
Microglia/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/metabolismo , Receptor 4 Toll-Like/fisiologia , Animais , Sobrevivência Celular/fisiologia , Células Cultivadas , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , Traumatismo por Reperfusão/patologia , Isquemia do Cordão Espinal/patologia , Receptor 4 Toll-Like/deficiência
17.
Appl Ergon ; 37(3): 305-310, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16171771

RESUMO

A reduction in stature (shrinkage) has been used as a measure of the load on the spine. Musculoskeletal effects of ageing may influence individual responses to compressive loading on the spine and the resultant loss in stature. The aim was to apply the technique of precision stadiometry for assessment of spinal shrinkage in a comparison of responses of two different age groups performing a regimen of circuit weight training. In all, 20 subjects (10 aged 18-25 and 10 aged 47-60 years) participated in the study. Each performed two sets of a 12-station circuit of exercises, the loading being established relative to individual capabilities. Recovery procedures using a semi-supine posture intervened between the two sets and again post-exercise; altogether seven measures of change in stature were obtained using precision stadiometry. The two groups showed a similar pattern of spinal shrinkage, losses in stature being greater for the first set compared to the later set of exercises. Subjects gained height whilst in the formal recovery posture, but responses were inconsistent during warm-up, cool-down and active recovery. Irrespective of age, the spine was less responsive to loading as the duration of activity was increased. It was concluded that provided loading is related to individual capability, healthy older operators are not necessarily compromised by their age in activities that include handling and lifting weights.


Assuntos
Coluna Vertebral/fisiologia , Suporte de Carga/fisiologia , Adolescente , Adulto , Estatura , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Reino Unido , Levantamento de Peso
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