RESUMEN
OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication of thoracoabdominal aortic aneurysm repair. We aim to characterize current practices pertaining to SCI prevention and treatment across Canada. METHODS: Two questionnaires were developed by the Canadian Thoracic Aortic Collaborative and the Canadian Cardiovascular Critical Care Society targeting aortic surgeons and intensivists. A list of experts in the management of patients at risk of SCI was developed, with representation from each of the Canadian centers that perform complex aortic surgery. RESULTS: The response rate was 91% for both intensivists (21/23), and from cardiac and vascular surgeons (39/43). Most surgeons agreed that staging is important during endovascular repair of extent II thoracoabdominal aortic aneurysm (60%) but not for open repair (34%). All of the surgeons felt prophylactic lumbar drains were effective in reducing SCI, whereas only 66.7% of intensivists felt that lumbar drains were effective (P < .001). There was consensus among surgeons over when to employ lumbar drains. A majority of surgeons preferred to keep the hemoglobin over 100 g/L if the patient demonstrated loss of lower-extremity function, whereas most intensivists felt a target of 80 g/L was adequate (P < .001). Management of perioperative antihypertensives, use of intraoperative adjuncts, and management of venous thromboembolism prophylaxis in the presence of a lumbar drain, were highly variable. CONCLUSIONS: We observed some consensus but considerable variability in the approach to SCI prevention and management across Canada. Future studies focused on the areas of variability may lead to more consistent and improved care for this high-risk population.
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Antihipertensivos/uso terapéutico , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular , Drenaje/métodos , Procedimientos Endovasculares , Región Lumbosacra , Complicaciones Posoperatorias , Isquemia de la Médula Espinal , Anciano , Actitud del Personal de Salud , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/métodos , Canadá/epidemiología , Consenso , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Femenino , Hemoglobinas/análisis , Humanos , Región Lumbosacra/patología , Región Lumbosacra/cirugía , Masculino , Paraparesia/diagnóstico , Paraparesia/etiología , Paraparesia/prevención & control , Atención Perioperativa/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/terapia , Ajuste de Riesgo/métodos , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/fisiopatología , Isquemia de la Médula Espinal/prevención & controlRESUMEN
OBJECTIVE: In our previous study, we found that lidocaine, infused through the abdominal aorta, could protect the spinal cord against the ischemia-reperfusion (I/R) injury caused by aortic occlusion. However, whether lidocaine protective effects have dose-dependent properties and its underlying mechanisms still remain unclear. This study was designed to investigate whether regionally infused lidocaine could dose-dependently protect spinal cord against I/R injury in rabbits and its underlying mechanism. METHODS: 46 New Zealand white rabbits were randomized into six groups: Group NS (normal saline control); Group L10 (lidocaine 10 mg/kg); Group L20 (lidocaine 20 mg/kg); Group L40 (lidocaine 40 mg/kg); Group L80 (lidocaine 80 mg/kg) and Group Sham. In Group NS, Group L10, Group L20, Group L40 and Group L80, spinal cord ischemia was induced by infrarenal aortic occlusion for 30 min. The sham group did not receive spinal cord ischemia. During the occlusion, normal saline or lidocaine at different doses was infused continuously through a catheter into the clamped abdominal aorta respectively. Neurologic behavior functions were assessed according to the Tarlov scale system at the moments of 0, 6, 24 and 48 h after reperfusion. The neural injuries were evaluated by the histological examination and the count of normal α-motor neurons in the ventral horn. The levels of excitatory amino acids (EAAs) in the spinal cord, including glutamate (Glu) and aspartic acid (Asp), were analyzed by high performance liquid chromatography with fluorescence detection. RESULTS: The Tarlov scales in the Group L20 and the Group L40 were significantly higher than those in the Group NS at 24 and 48 h after reperfusion (P < 0.05). 12.5 % animals in Group L40 and 25 % animals in Group L20 were paraplegic versus 75 % animals in Group NS at 48 h after reperfusion (P < 0.05). The median of normal α-motor neurons in the L20, L40 and L80 groups was 7.5, 9 and 5 respectively which was significantly higher than in the NS group (count 0, P < 0.05). The levels of L-ASP and L-Glu remarkably decreased in the Group L10 and the Group L40 compared to Group NS (P < 0.05). CONCLUSIONS: These data revealed that regional administration of lidocaine through the abdominal aorta can provide dose-dependent protection on spinal cord I/R in rabbits. Inhibition of EAA release may be one of the underlying mechanisms.
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Anestésicos Locales/administración & dosificación , Aminoácidos Excitadores/sangre , Infusiones Intraarteriales/métodos , Lidocaína/administración & dosificación , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Conejos , Distribución AleatoriaRESUMEN
BACKGROUND: Despite all efforts, spinal cord ischemia (SCI) is a relevant and feared complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Besides the established correlation of motor evoked potentials (MEPs) and SCI, the usage of biomarkers for early detection of SCI intraoperatively and postoperatively after TAAA surgery is scarcely described in literature. METHODS: The methods include retrospective assessment of 33 patients (48.48% male) undergoing open and endovascular TAAA repair between January 2017 and January 2018. Levels of the biomarkers neurone-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100 B were correlated with a decrease of the amplitude of the MEPs of more than 50%, indicating SCI. Linear mixed models were applied to test for differences in the biomarker levels between open and endovascular surgery and between different times of measurement. Post hoc analyses were performed using Tukey's multiple comparisons test. Logistic regression models were used to investigate the association between GFAP, NSE, and S100 B levels at different times and a significant decrease in MEP or in-hospital mortality. RESULTS: Altogether, 19 patients were treated by endovascular repair; 14 patients were treated by open repair; 5 patients were treated because of a type I TAAA; 7 received treatment because of a type II TAAA; 7, 10, and 4 patients received type III, IV, or V TAAA repair, respectively. In-hospital mortality was 18.18% (n = 6); 5 of these patients were treated because of symptomatic TAAA. MEP decrease could be observed in 18 cases (54.5%), with 16 (48.4%) recovering during the intervention. SCI could be observed in 9.09% (n = 3), 2 endovascular repairs leading to paraplegia and one open repair leading to paraparesis. All biomarkers showed increasing levels over time, with no statistically significant difference between open and endovascular repair. The difference in NSE and S100 B levels between the different times of measurements was statistically significant (P < 0.0001, P = 0.0017, respectively). In a univariable logistic regression analysis, no correlation with the end points "significant decrease in MEP" or "in-hospital mortality" was observed for any of the assessed biomarkers. CONCLUSIONS: SCI-related biomarkers, namely NSE and S100 B, show a relevant increase directly after open and endovascular TAAA surgery, while no clear association between these biomarker levels and an intraoperatively measurable indicator for SCI could be observed.
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Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Proteína Ácida Fibrilar de la Glía/sangre , Fosfopiruvato Hidratasa/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Isquemia de la Médula Espinal/sangre , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Torácica/sangre , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/mortalidad , Biomarcadores/sangre , Implantación de Prótesis Vascular/mortalidad , Procedimientos Endovasculares/mortalidad , Potenciales Evocados Motores , Femenino , Mortalidad Hospitalaria , Humanos , Monitorización Neurofisiológica Intraoperatoria , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Isquemia de la Médula Espinal/diagnóstico , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). METHODS: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. RESULTS: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. CONCLUSIONS: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.
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Aneurisma de la Aorta Torácica/cirugía , Biomarcadores/líquido cefalorraquídeo , Técnicas Electroquímicas/métodos , Fosfopiruvato Hidratasa/sangre , Isquemia de la Médula Espinal/líquido cefalorraquídeo , Biomarcadores/sangre , Drenaje , Humanos , Ácido Láctico/sangre , Ácido Láctico/líquido cefalorraquídeo , Proteínas S100/sangre , Proteínas S100/líquido cefalorraquídeo , Isquemia de la Médula Espinal/sangreRESUMEN
Abstract Objective: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). Methods: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. Results: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. Conclusions: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.
Asunto(s)
Humanos , Fosfopiruvato Hidratasa/sangre , Biomarcadores/líquido cefalorraquídeo , Aneurisma de la Aorta Torácica/cirugía , Isquemia de la Médula Espinal/líquido cefalorraquídeo , Técnicas Electroquímicas/métodos , Biomarcadores/sangre , Proteínas S100/líquido cefalorraquídeo , Proteínas S100/sangre , Drenaje , Ácido Láctico/líquido cefalorraquídeo , Ácido Láctico/sangre , Isquemia de la Médula Espinal/sangreRESUMEN
INTRODUCTION:: Despite advances in perioperative critical care and surgical technique, spinal cord ischemia remains a devastating complication of thoracic and thoracoabdominal aortic aneurysm repair. Biochemical markers present in peripheral blood and cerebrospinal fluid (CSF) may be useful in assessing spinal cord injury. We systematically analyze and report the role of all reported biochemical markers that have been used in assessing and diagnosing spinal cord ischemia in thoracic and thoracoabdominal aortic aneurysm repair. METHODS:: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for this review. Published literature was searched to identify all studies reporting on the use of biochemical markers in thoracoabdominal aortic aneurysm repair in the assessment of spinal cord ischemia. Marker-specific and patient-specific data were extracted from all studies and where possible, subgroup analysis was performed on marker-specific data sets. RESULTS:: Fourteen studies of 321 patients undergoing thoracic and thoracoabdominal aortic aneurysm repair were eligible for further analysis. Seven distinct biochemical markers were used in both CSF and blood samples: S100B proteins (S100B), neurone-specific enolase, lactate dehydrogenase, glial fibrillary acidic protein (GFAp), neurofilament triplet protein (NFL) and Tau protein, and glucose. There was substantial evidence demonstrating the heightened levels of S100, NFL, and GFAp in CSF in patients with spinal cord ischemia. There is however, wide variability in the correlation of the same 6 biochemical markers in peripheral blood and spinal cord ischemia. CONCLUSIONS:: In patients with spinal cord injury, dramatic rises occur with S100B, NFL, and GFAp in CSF. However, further work is needed if biochemical markers are to impact on the future of thoracoabdominal aortic aneurysm repair.
Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Torácica/sangre , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/fisiopatología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Factores de Riesgo , Isquemia de la Médula Espinal/diagnóstico , Isquemia de la Médula Espinal/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabdominal aortic aneurysms. For prevention and early treatment of spinal ischemia, intraoperative monitoring of spinal cord integrity is essential. This study was intended to improve recognition of SCI through a combination of transcranial motor-evoked potentials (tc-MEPs), serum markers, and innovative breath analysis. METHODS: In 9 female German Landrace pigs, tc-MEPs were captured, markers of neuronal damage were determined in blood, and volatile organic compounds (VOCs) were analyzed in exhaled air. After thoraco-phrenico-laparotomy, SCI was initiated through sequential clamping (n = 4) or permanently ligating (n = 5) SAs of the abdominal and thoracic aorta in caudocranial orientation until a drop in the tc-MEPs to at least 25% of the baseline was recorded. VOCs in breath were determined by means of solid-phase microextraction coupled with gas chromatography-mass spectrometry. After waking up, clinical and neurological status was evaluated (Tarlov score). Spinal cord histology was obtained in postmortem. RESULTS: Permanent vessel ligature induced a worse neurological outcome and a higher number of necrotic motor neurons compared to clamping. Changes of serum markers remained unspecific. After laparotomy, exhaled acetone and isopropanol showed highest concentrations, and pentane and hexane increased during ischemia-reperfusion injury. CONCLUSIONS: To mimic spinal ischemia occurring in humans during aortic aneurysm repair, animal models have to be meticulously evaluated concerning vascular anatomy and function. Volatiles from breath indicated metabolic stress during surgery and oxidative damage through ischemia reperfusion. Breath VOCs may provide complimentary information to conventional monitoring methods.
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Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Biomarcadores/sangre , Pruebas Respiratorias/métodos , Potenciales Evocados Motores , Monitorización Neurofisiológica Intraoperatoria/métodos , Isquemia de la Médula Espinal/diagnóstico , Compuestos Orgánicos Volátiles/metabolismo , Animales , Constricción , Modelos Animales de Enfermedad , Femenino , Cromatografía de Gases y Espectrometría de Masas , Ligadura , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Estrés Oxidativo , Valor Predictivo de las Pruebas , Microextracción en Fase Sólida , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/fisiopatología , Sus scrofa , Factores de TiempoRESUMEN
OBJECTIVE: This study examined effects and functional outcome of recombinant human erythropoietin (rhEPO) and carbamylated erythropoietin fusion protein (cEPO-FC) preconditioning in a rabbit model for spinal cord ischemia and resulting paraplegia. This model was chosen because only a small surgical effect is needed to cause paraplegia in rabbits, which facilitates postoperative observation of animals. METHODS: Anesthetized but spontaneously breathing New Zealand White rabbits randomly received cEPO-FC (50 µg/kg; n = 8), rhEPO (5000 IU/kg; n = 10), or vehicle (control; n = 10) 30 minutes before and after infrarenal aortic clamping. Ideal clamping time of 22 minutes was identified from preceding clamping tests (15-25 minutes). Postoperative observation time was 96 hours. Spinal cord function was assessed by neurologic evaluation of hind limb motor function every 12 hours using a modified Tarlov score. Spinal cord tissue damage was evaluated after 96 hours using hematoxylin and eosin, elastica van Gieson, Nissl, Masson-Goldner, and hemosiderin staining. Plasma levels of cell senescence markers stathmin, chitinase 1/3, elongation factor 1-α were determined. RESULTS: Rabbits that received rhEPO showed significant improvement of spontaneous lower limb movements until 36 hours of reperfusion and improved histologic scores upon examination of the lumbar spinal cord compared with the control group. In contrast, cEPO-FC treatment showed comparable outcome to the control group concerning movements of the lower limbs and histology. Senescence markers were elevated in the control group, but not in the treatment groups, except for chitinase 3 in the rhEPO group. Only stathmin showed no significant effect. Markers for senescence might increase after acute ischemic injury. Attenuation of senescence markers might not come alone from improvement of the spinal cord. CONCLUSIONS: Preconditioning with rhEPO attenuates ischemia/reperfusion injury of the spinal cord, whereas the carbamylated derivative (cEPO-FC) showed no positive effect on spinal cord function.
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Eritropoyetina/análogos & derivados , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/prevención & control , Isquemia de la Médula Espinal/prevención & control , Médula Espinal/efectos de los fármacos , Animales , Biomarcadores/sangre , Senescencia Celular/efectos de los fármacos , Quitinasas/sangre , Modelos Animales de Enfermedad , Eritropoyetina/farmacología , Masculino , Actividad Motora , Examen Neurológico , Paraplejía/fisiopatología , Paraplejía/prevención & control , Factor 1 de Elongación Peptídica/sangre , Conejos , Proteínas Recombinantes/farmacología , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Médula Espinal/metabolismo , Médula Espinal/patología , Médula Espinal/fisiopatología , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/patología , Isquemia de la Médula Espinal/fisiopatología , Estatmina/sangre , Factores de TiempoRESUMEN
BACKGROUND: Cilostazol is a phosphodiesterase inhibitor that has anti-inflammatory potential in addition to vasodilator and antiplatelet effects. The aim of this study was to determine the influence of cilostazol on biochemical markers of oxidative damage, proinflammatory cytokine release, and spinal cord injury after transient aortic occlusion in rats. METHODS: Animals were randomized into 3 groups. Sham group rats were subjected to laparotomy without aortic occlusion. Control group rats were pretreated with intraperitoneal dimethyl sulfoxide, and cilostazol group rats received intraperitoneal cilostazol (20 mg/kg/day) for 3 days before the induction of ischemia. Ischemia was induced by clamping of the infrarenal aorta, and 48 hours after reperfusion, Tarlov grades were assessed and spinal cord conduction velocities (SCCVs) were measured using epidural electrical stimulation. Erythrocyte superoxide dismutase (SOD) and catalase activities and plasma malondialdehyde, serum tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels were analyzed. Spinal cord histopathology was examined to determine neuronal damage and tissue inflammation. RESULTS: Aortic occlusion caused significant increases in SOD, catalase activities, and malondialdehyde and cytokine levels accompanied by spinal cord injury. Cilostazol significantly reduced malondialdehyde levels but did not significantly alter the activations of antioxidant enzymes, levels of proinflammatory cytokines, or histologic severity of inflammation. The differences regarding the results of Tarlov grading, SCCVs, and neuronal viability between the ischemic and cilostazol pretreated groups were statistically nonsignificant. CONCLUSION: The present experimental study indicated that cilostazol pretreatment used in this study before aortic occlusion decreased lipid peroxidation, which may be related to the reduction of reactive oxygen species. Cilostazol did not significantly suppress systemic cytokine release and prevent spinal cord inflammation and injury; however, it did show some benefit. Additional investigations might be needed to determine the critical dose of cilostazol for clarifying the protective role of this drug in spinal cord ischemia/reperfusion injury.
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Antioxidantes/farmacología , Aorta Abdominal/cirugía , Citocinas/sangre , Mediadores de Inflamación/sangre , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/prevención & control , Isquemia de la Médula Espinal/prevención & control , Médula Espinal/efectos de los fármacos , Tetrazoles/farmacología , Animales , Antiinflamatorios/farmacología , Aorta Abdominal/fisiopatología , Biomarcadores/sangre , Supervivencia Celular/efectos de los fármacos , Cilostazol , Constricción , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Conducción Nerviosa/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/sangre , Daño por Reperfusión/etiología , Daño por Reperfusión/inmunología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Médula Espinal/inmunología , Médula Espinal/metabolismo , Médula Espinal/patología , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/inmunología , Isquemia de la Médula Espinal/patología , Isquemia de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Paraplegia after thoracoabdominal aortic surgery is a devastating complication attributed to motor neurons loss and dysfunction, due to spinal cord ischemia. ß-Catenin is a protein that has been associated with cell survival and healing and many studies have correlated this protein with late ischemic preconditioning (IPC). Herein we investigate the potential contribution of ß-catenin in an early IPC animal model, and its relationship with heat shock protein 70 (Hsp70), suggesting a possible role of this protein as a first window of protection. METHODS: A total of 42 pigs were used in an experimental thoracoabdominal aortic occlusion model. Twelve animals were used for neurologic evaluation and were randomly assigned to 2 groups (A and B). The remaining 30 animals were used in experiments for biologic measurements and innunohistochemical studies, and were randomly assigned to 5 groups (1-5). Western blotting analysis and immunoprecipitations were performed to study the levels of ß-catenin and its binding relationship with Hsp70. The cellular distribution of ß-catenin at various time-points was investigated by immunohistochemical studies. RESULTS: According to neurologic evaluation, the animals in the IPC+ischemia group had significantly better neurologic scores compared with those in the ischemia group, indicating a protective role for IPC. The biologic measurements demonstrated a significant (P=0.03) increase in ß-catenin levels and translocation of the protein in the nucleus at the end of ischemic preconditioning. CONCLUSIONS: Our results suggest a significant role of ß-catenin in early IPC protection of spinal cord after thoracoabdominal occlusion, as IPC seems to trigger the activation of the ß-catenin stabilized fraction and, thus, its survival pathway.
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Enfermedades de la Aorta/terapia , Precondicionamiento Isquémico/métodos , Isquemia de la Médula Espinal/prevención & control , Médula Espinal/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares/efectos adversos , beta Catenina/sangre , Animales , Enfermedades de la Aorta/sangre , Modelos Animales de Enfermedad , Periodo Posoperatorio , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/etiología , Porcinos , Resultado del TratamientoRESUMEN
Safflower yellow (SY) is the safflower extract and is the one of traditional Chinese medicine. The aim of the present work was to investigate the effect of SY on spinal cord ischemia reperfusion injury (SCIRI) in rabbits. The models of spinal cord ischemia reperfusion (SI/R) were constructed, and the degree of the post-ischemic injury was assessed by means of the neurological deficit scores and plasma levels of lipid peroxidation reactioin and neuronal morphologic changes. SCIRI remarkably affected the functional activities of the hind limbs and activated lipid peroxidation reaction. SY could attenuate apoptosis and SCIRI by enhancing Bcl-2 expression and inhibiting Bax and caspase-3 activation.
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Chalcona/análogos & derivados , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Isquemia de la Médula Espinal/complicaciones , Isquemia de la Médula Espinal/tratamiento farmacológico , Animales , Células del Asta Anterior/efectos de los fármacos , Células del Asta Anterior/enzimología , Células del Asta Anterior/patología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Forma de la Célula/efectos de los fármacos , Chalcona/farmacología , Chalcona/uso terapéutico , Miembro Posterior/efectos de los fármacos , Miembro Posterior/fisiopatología , Etiquetado Corte-Fin in Situ , Interleucina-8/sangre , Masculino , Malondialdehído/metabolismo , Fitoterapia , Conejos , Daño por Reperfusión/sangre , Daño por Reperfusión/enzimología , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/enzimología , Superóxido Dismutasa/metabolismo , Factores de Tiempo , Signos Vitales/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Acute normovolemic hemodilution (ANH) is currently performed during thoracoabdominal aortic surgery. However, the effects of ANH on spinal cord ischemic injury are currently unknown. Because hemodilution below a certain level of hematocrit (Hct) aggravates the neurological damage after cerebral ischemia, we hypothesized that ANH may increase neurological damage after spinal cord ischemia. The aim of these experiments was to determine the effects of ANH on spinal cord ischemic injury. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to 1 of the following 3 groups: no hemodilution (group C), target Hct level of 30% (group HD30), and target Hct level of 25% (group HD25). ANH was performed upon withdrawal of blood and simultaneous replacement with the same volume with hydroxyethyl starch. Spinal cord ischemia and reperfusion were induced by using a balloon-tipped catheter placed in the descending thoracic aorta, and changes in mean arterial blood pressure were recorded. Neurological function of the hindlimbs was evaluated for 7 days and recorded using a motor deficit score (MDS) (0 = normal; 5 = complete paraplegia). The number of motor neurons within the spinal cord was counted after final MDS evaluation. RESULTS: Group HD25 developed hypotension during the latter part of the ANH procedure. Group C and group HD30 experienced 3 minutes of reperfusion hypotension, whereas 6 minutes of hypotension was observed in group HD25. Two rats in group HD25 died during the experimental period. Seven days after reperfusion, the MDS of group C, group HD30, and group HD25 was 1.0 (0.5-2.0), 1.0 (0.5-2.0), and 4.0 (2.8-4.2) (median [95% confidence interval]), respectively. Group HD25 showed significantly higher MDS compared with group C (corrected P = 0.0018; 95% CI for median difference = 1.0-3.5). Motor neuron numbers in the anterior horns of group C, group HD30, and group HD25 were 26.5 (25.0-27.5), 23.5 (22.0-26.5), and 12.5 (8.4-16.6) (median [95% CI]), respectively. Motor neuron numbers of group HD25 were significantly lower than those of group C (corrected P < 0.0001; 95% CI for median difference = 9.0-18.0). CONCLUSION: The results of the present study indicate that intraoperative ANH to an Hct of 25%, combined with coincident hypotension, caused a delayed recovery of baseline mean arterial blood pressure during the reperfusion period and aggravated neurological outcome after spinal cord ischemia.
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Volumen Sanguíneo , Hemodilución/efectos adversos , Derivados de Hidroxietil Almidón/toxicidad , Actividad Motora , Neuronas Motoras/patología , Sustitutos del Plasma/toxicidad , Isquemia de la Médula Espinal/etiología , Animales , Presión Sanguínea , Cateterismo , Modelos Animales de Enfermedad , Hematócrito , Hipotensión/etiología , Hipotensión/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/patología , Isquemia de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Hemoglobin Q-Iran is a rare variant which has not been described in association with alpha-thalassemia to date. We present the case of a Turkish patient who developed spinal ischemia. METHODS: Spinal ischemia was diagnosed clinically, via magnetic resonance imaging and angiographically. Blood samples were analyzed by high performance liquid chromatography, electrophoresis, gene sequencing, hematological and biochemical analysis. RESULTS: We detected hemoglobin Q-Iran in association with alpha-thalassemia. The same hemoglobinopathy was detected in two members of the patient's family. CONCLUSIONS: As various differential diagnosis approaches failed to reveal the cause of spinal ischemia, the combined hemoglobinopathy was eventually postulated.
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Hemoglobinas Anormales/análisis , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/complicaciones , Talasemia alfa/sangre , Talasemia alfa/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Isquemia de la Médula Espinal/diagnóstico , Isquemia de la Médula Espinal/genética , Turquía , Talasemia alfa/genéticaRESUMEN
PURPOSE: To describe a simple, noninvasive technique to detect changes in oxygen saturation at the level of the spinal cord and to suggest its suitability for individualized blood pressure management during and after thoracoabdominal aneurysm repair. CASE REPORT: A 53-year-old man with a history of multiple arch and thoracic aortic procedures underwent staged hybrid treatment of a large TAAA due to chronic dissection from the distal aortic arch into the iliac arteries. During the procedures, near-infrared spectroscopy (NIRS) sensors were applied over the 10th thoracic vertebra for continuous monitoring of tissue oxygen saturation (S(s)O(2)) during endovascular repair. After stent-graft deployment, mean S(s)O(2) decreased significantly. Moreover, the relationship between S(s)O(2) and arterial blood pressure became linear, reflecting pressure dependency of spinal cord perfusion after stent deployment. CONCLUSION: These data show that NIRS monitors post-endograft changes in S(s)O(2) that were strongly related to arterial blood pressure. Regional NIRS monitoring at the vertebral level may function as a valuable noninvasive guide to the management of blood pressure during thoracoabdominal aneurysm repair, both intra- and postoperatively.
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Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Monitoreo Intraoperatorio/métodos , Oximetría , Oxígeno/sangre , Espectroscopía Infrarroja Corta , Isquemia de la Médula Espinal/diagnóstico , Presión Sanguínea , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/fisiopatologíaAsunto(s)
Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Monitoreo Intraoperatorio/métodos , Oximetría , Oxígeno/sangre , Isquemia de la Médula Espinal/diagnóstico , Presión Sanguínea , Humanos , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Espectroscopía Infrarroja Corta , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/fisiopatologíaRESUMEN
The protective effects of diltiazem were examined in a rabbit model of spinal cord ischaemia-reperfusion induced by infrarenal aortic occlusion for 30 min. In the diltiazem group (n = 6), an intravenous infusion (2 microg/kg per min) was started 10 min before ischaemia induction; normal saline solution was infused in the control group (n = 6). Neurological function was assessed using modified Tarlov criteria 24 h after surgery. Plasma samples were analysed for interleukin (IL)-6 and IL-10. Spinal tissue was analysed for malondialdehyde, nitric oxide and reduced glutathione activities. Tarlov scores of the diltiazem-treated rabbits indicated significantly improved hind-limb motor function compared with the control group. The diltiazem group also had better quantitative and qualitative histopathological findings. Diltiazem infusion significantly reduced IL-6 levels 3 and 24 h after reperfusion compared with the control group. The mean IL-10 level in the diltiazem group was significantly higher than in the control group 24 h after reperfusion. It is concluded that diltiazem has cytoprotective and anti-inflammatory properties, leading to reduced spinal cord injury.
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Antiinflamatorios/uso terapéutico , Diltiazem/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Isquemia de la Médula Espinal/tratamiento farmacológico , Animales , Glutatión/metabolismo , Interleucina-10/sangre , Interleucina-6/sangre , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Conejos , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/patología , Isquemia de la Médula Espinal/fisiopatologíaRESUMEN
OBJECTIVE: Detecting spinal cord ischemia early during replacement of the thoracoabdominal aorta remains a challenge. In a high risk population, we have re-evaluated the potential impact of ischaemia/damage markers (S100, lactate) in the peripheral blood and CSF for perioperative patient management. PATIENTS AND METHODS: Thirteen patients undergoing replacement of the thoracoabdominal aorta (6 female, age 63 (27-71)) with continuous CSF pressure monitoring and drainage were entered into the study. A total of 485 CSF (C) and serum (S) samples were collected and analysed for S100, lactate and glucose. RESULTS: Two patients suffered from spinal cord injury (SCI) (15%). During and early after surgery, there was a strong correlation between C-S100 levels (r=0.79) and C-lactate levels (r=0.77) with time in patients with SCI. In patients with SCI C-lactate levels increased soon after aortic cross-clamping, whereas C-S100 levels did not become significantly elevated until 6 hours after cross-clamping. CONCLUSION: An increase of C-lactate occurs much earlier than the increase in C-S100 in patients with SCI. Both parameters may be used to adjust protective and therapeutic measures intra- and postoperatively.
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Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/efectos adversos , Ácido Láctico/líquido cefalorraquídeo , Monitoreo Intraoperatorio/métodos , Proteínas S100/líquido cefalorraquídeo , Isquemia de la Médula Espinal/diagnóstico , Adulto , Anciano , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proyectos de Investigación , Proteínas S100/sangre , Traumatismos de la Médula Espinal/líquido cefalorraquídeo , Traumatismos de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/prevención & control , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/líquido cefalorraquídeo , Isquemia de la Médula Espinal/etiología , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: It is not well established whether insulin protects against ischemic spinal cord injury. We examined the effects of a single dose of insulin that corrects mild hyperglycemia on the outcome after transient spinal cord ischemia in rabbits. METHODS: We assigned rabbits to four groups (n = 8 in each); untreated control (C) group, preischemic insulin (Pre-I) group, preischemic insulin with glucose (GI) group (glucose concentrations were maintained at levels similar to the C group by the administration of glucose), and postischemic insulin (Post-I) group. Insulin (0.5 IU/kg) was administered 30 min before ischemia in the Pre-I and GI groups, and just after reperfusion in the Post-I group. Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Neurologic and histopathologic evaluations were performed 7 days after ischemia. RESULTS: The mean blood glucose concentration before ischemia in the Pre-I group (118 mg/dL) was significantly lower than in the other three groups (158-180 mg/dL) and those of 30 min after reperfusion in the Pre-I (92 mg/dL) and Post-I (100 mg/dL) groups were significantly lower than in the C (148 mg/dL) and GI (140 mg/dL) groups. The motor function score and number of normal neurons in the anterior lumbar spinal cord in the Pre-I group were significantly greater than in the other three groups. CONCLUSIONS: These results suggest that a relatively small dose of preischemic insulin protects against ischemic spinal cord injury, and that the protective effects result from tight glycemic control before ischemia.
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Índice Glucémico/efectos de los fármacos , Insulina/uso terapéutico , Isquemia de la Médula Espinal/sangre , Isquemia de la Médula Espinal/prevención & control , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Índice Glucémico/fisiología , Insulina/farmacología , Precondicionamiento Isquémico/métodos , Conejos , Factores de TiempoRESUMEN
Prevention of paraplegia remains an imperative issue in thoracoabdominal aortic surgery. The aim of this study was to assess the efficacy of a prophylactic magnesium infusion in a rat spinal cord ischemia model and to demonstrate spinal blood flow increase caused by the infusion. The study was conducted in two parts. Firstly, the neuroprotective effect of magnesium was assessed using a rat model with two different ischemic times: 10 min and 14 min. Spinal cord ischemia was induced by occlusion of the descending aorta. Rats in the treatment group were given a 100 mg/kg magnesium sulfate infusion before ischemia. Secondly, relative changes in spinal cord blood flow before and during ischemia were recorded using the laser Doppler flowmetry technique. Changes in blood flow were compared between the magnesium and control groups. Rats pretreated with magnesium showed good overall recovery after both 10 min (incidence of paraplegia 62.5% control vs. 37.5% Mg, n = 8 each) and 14 min (85.7% control vs. 57.1% Mg, n = 7 each) of ischemia, although the differences compared with controls were statistically insignificant. However, the magnesium group showed significantly better neurological performance during the early postischemic period. Comparison of changes in spinal circulation revealed less reduction in blood flow during ischemia in the magnesium-treated group. In conclusion, magnesium may have potential prophylactic benefits during ischemia by exerting a neuroprotective effect through vasodilation of the spinal cord vasculature. To our knowledge, this vasodilatory effect on the spinal cord has not previously been investigated. Optimization of the treatment regimen, however, is required.