Lung injury in patients age 75 years and older with the use of polymethylmethacrylate fenestrated pedicle screws.

BACKGROUND CONTEXT: Pulmonary complications in patients age 75 years and older who undergo spinal fusion may have catastrophic consequences. The use of augmentation techniques with polymethylmethacrylate (PMMA) have been associated with pulmonary damage. The use of fenestrated pedicle screws augmented with PMMA may increase the risk of lung injury in this population. PURPOSE: To investigate whether the use of PMMA-augmented screws is correlated with increased lung injury in patients undergoing instrumented lumbar spinal fusion. STUDY DESIGN: A nonrandomized, prospective, case-controlled clinical study was carried out. PATIENT SAMPLE: We included 50 consecutive patients: 25 classifieds as patients who required PMMA-augmented screws in lumbar spinal fusion, and 25 classifieds as control participants because they underwent uncemented instrumented spinal fusion. OUTCOME MEASURES: We compare the incidence of the event, lung damage, in both groups by measuring a series of parameters: arterial blood gas, transesophageal echocardiography, urinary desmosine, and chest radiograph. The epidemiological parameters analyzed were age, sex, body mass index, status as a smoker, and number of cement leaks. METHODS: Changes in pulmonary damage markers were described in both groups of patients, comparing postsurgery values with baseline values. In control participants, each change was evaluated for the total number of patients. All changes are indicated in this report by mean differences for quantitative variables and by differing proportions for qualitative variables, with 95% confidence intervals provided for all values. RESULTS: There was an increase in postinstrumentation PaO2 (arterial partial pressure of oxygen) in both groups, probably related to the use of mechanical ventilation and recruitment maneuvers. Even though the group that required augmentation had lower baseline levels, the difference between groups was not statistically significant. On transesophageal echocardiographs, we observed scattered small, snowflake-like emboli, and bright echo signals appeared in the right atrium during PMMA injection. Signal density was constant but gradually faded away when PMMA injection ended. No participants in the group without augmentation had radiological complications. Overall, desmosine levels increased in both groups, and the rise was similar in both. There was a slight average increase in urine desmosine levels after instrumentation and progressively continues to rise until 24 hours after instrumentation, with a subsequent decrease at 72 hours. Comparing the two groups, we found no statistically significant differences at any time. CONCLUSIONS: We were not able to identify a significant difference in urine desmosine levels associated with the augmentation of with fenestrated pedicle screws with PMMA. Despite comparing patients age 75 years or older with a younger group, we found no clinical, analytical, or gasometric data indicating lung damage in patients who had augmentation.

The effect of anesthetic preconditioning with sevoflurane on intracellular signal-transduction pathways and apoptosis, in a lung autotransplant experimental model / O efeito do pré-condicionamento anestésico com sevoflurano sobre as vias de transdução de sinal intracelular e a apoptose, em modelo experimental de autotransplante pulmonar

Abstract Background: Anesthetic pre-conditioning attenuates inflammatory response during ischemia-reperfusion lung injury. The molecular mechanisms to explain it are not fully understood. The aim of our investigation was to analyze the molecular mechanism that explain the anti-inflammatory effects of anesthetic pre-conditioning with sevoflurane focusing on its effects on MAPKs (mitogen-activated protein kinases), NF-κB (nuclear factor kappa beta) pathways, and apoptosis in an experimental lung autotransplant model. Methods: Twenty large white pigs undergoing pneumonectomy plus lung autotransplant were divided into two 10-member groups on the basis of the anesthetic received (propofol or sevoflurane). Anesthetic pre-conditioning group received sevoflurane 3% after anesthesia induction and it stopped when one-lung ventilation get started. Control group did not receive sevoflurane in any moment during the whole study period. Intracellular signal-transduction pathways (MAPK family), transcription factor (NF-κB), and apoptosis (caspases 3 and 9) were analyzed during experiment. Results: Pigs that received anesthetic pre-conditioning with sevoflurane have shown significant lower values of MAPK-p38, MAPK-P-p38, JNK (c-Jun N-terminal kinases), NF-κB p50 intranuclear, and caspases (p < 0.05) than pigs anesthetized with intravenous propofol. Conclusions: Lung protection of anesthetic pre-conditioning with sevoflurane during experimental lung autotransplant is, at least, partially associated with MAPKs and NF κB pathways attenuation, and antiapoptotic effects.

Resumo Justificativa: O pré-condicionamento anestésico atenua a resposta inflamatória durante a lesão de isquemia-reperfusão do pulmão. Os mecanismos moleculares para explicá-lo não são totalmente compreendidos. O objetivo de nossa investigação foi analisar o mecanismo molecular que explica os efeitos anti-inflamatórios do pré-condicionamento anestésico com sevoflurano, enfocar seus efeitos sobre as proteínas quinases ativadas por mitógenos (MAPKs), o fator nuclear kappa beta (NF-κB) e a apoptose em modelo experimental de autotransplante pulmonar. Métodos: Vinte porcos Large White submetidos à pneumonectomia e autoimplante de pulmão foram divididos em dois grupos de 10 membros com base no anestésico recebido (propofol ou sevoflurano). O grupo de pré-condicionamento anestésico recebeu sevoflurano a 3% após a indução da anestesia, que foi descontinuado quando a ventilação monopulmonar foi iniciada. O grupo controle não recebeu sevoflurano em qualquer momento durante todo o período do estudo. As vias de transdução de sinal intracelular (família MAPK), o fator de transcrição (NF-κB) e a apoptose (caspases 3 e 9) foram analisados durante o experimento. Resultados: Os suínos que receberam pré-condicionamento anestésico com sevoflurano apresentaram valores mais baixos de MAPK-p38, MAPK-P-p38, c-Jun N-terminal quinases (JNK), NF-κB p50 intranuclear e caspases (p < 0,05) do que os suínos anestesiados com propofol intravenoso. Conclusões: A proteção pulmonar do pré-condicionamento anestésico com sevoflurano durante o autotransplante pulmonar experimental está, pelo menos, parcialmente associada à atenuação das vias de MAPKs e NF κB e aos efeitos antiapoptóticos.

[The effect of anesthetic preconditioning with sevoflurane on intracellular signal-transduction pathways and apoptosis, in a lung autotransplant experimental model]. / O efeito do pré­condicionamento anestésico com sevoflurano sobre as vias de transdução de sinal intracelular e a apoptose, em modelo experimental de autotransplante pulmonar.

BACKGROUND: Anesthetic pre-conditioning attenuates inflammatory response during ischemia-reperfusion lung injury. The molecular mechanisms to explain it are not fully understood. The aim of our investigation was to analyze the molecular mechanism that explain the anti-inflammatory effects of anesthetic pre-conditioning with sevoflurane focusing on its effects on MAPKs (mitogen-activated protein kinases), NF-κB (nuclear factor kappa beta) pathways, and apoptosis in an experimental lung autotransplant model. METHODS: Twenty large white pigs undergoing pneumonectomy plus lung autotransplant were divided into two 10-member groups on the basis of the anesthetic received (propofol or sevoflurane). Anesthetic pre-conditioning group received sevoflurane 3% after anesthesia induction and it stopped when one-lung ventilation get started. Control group did not receive sevoflurane in any moment during the whole study period. Intracellular signal-transduction pathways (MAPK family), transcription factor (NF-κB), and apoptosis (caspases 3 and 9) were analyzed during experiment. RESULTS: Pigs that received anesthetic pre-conditioning with sevoflurane have shown significant lower values of MAPK-p38, MAPK-P-p38, JNK (c-Jun N-terminal kinases), NF-κB p50 intranuclear, and caspases (p<0.05) than pigs anesthetized with intravenous propofol. CONCLUSIONS: Lung protection of anesthetic pre-conditioning with sevoflurane during experimental lung autotransplant is, at least, partially associated with MAPKs and NF κB pathways attenuation, and antiapoptotic effects.

Procedimiento de autotrasplante pulmonar en el cerdo como modelo experimental para el estudio del síndrome de isquemia-reperfusión / Experimental Swine Lung Autotransplant Model to Study Lung Ischemia-Reperfusion Injury

Introducción: El daño pulmonar agudo por isquemia reperfusión (IR) ha sido estudiado fundamentalmenteen modelos experimentales y clínicos con IR fría. Son limitados los estudios que profundizan en lasalteraciones bioquímicas durante la IR normotérmica (caliente). El objetivo del este trabajo es presentarun modelo de autotrasplante pulmonar en cerdo para el estudio de las fases más precoces del síndromede IR normotérmica pulmonar.Animales y métodos: Seis cerdos de la raza Large-White fueron sometidos a neumonectomía izquierda,lobectomía craneal ex situ, reimplantación del lóbulo caudal y reperfusión del mismo durante 30 min.Durante el procedimiento se analizaron diferentes parámetros para identificar cambios hemodinámicos,gasométricos y bioquímicos en el modelo. El estudio estadístico se realizó con pruebas no paramétricas.Resultados: Tras la isquemia, se observó en tejido pulmonar un aumento significativo (p < 0,05) de metabolitosde peroxidación lipídica, de citoquinas y quemoquinas proinflamatorias (TNF- , IL-1 y MCP-1),de actividad leucocitaria (mieloperoxidasa o MPO), de actividad óxido nítrico sintasa inducible y de laproteína quinasaMAPKp38, mientras que se observóundescenso de actividad tisular de las formas constitutivasde NOS y de monóxido de carbono sérico. Estas alteraciones se mantuvieron o acentuaron durantela reperfusión, donde se observó también una mayor actividad tisular hemo-oxigenasa constitutiva.Conclusiones: Se presenta un procedimiento experimental de IR normotérmica pulmonar describiendo enprofundidad cambios hemodinámicos, gasométricos y bioquímicos. Tanto el modelocomolos parámetrosanalizados podrían ser útiles en el estudio de nuevas terapias moduladoras del da˜no pulmonar agudo ensituaciones clínicas de IR normotérmica(AU)

Introduction: Ischemia-reperfusion (IR) lung injury has been investigated extensively on clinical andexperimental models of cold ischemia. However, relatively few studies examine the detailed biochemicalchanges occurring during normothermic (warm) IR.The objective of this work was to establish an experimental lung autotransplant model to be carried outon pigs in order to study the early stages of normothermic lung IR.Animals y methods: Six Large-White pigs underwent a lung autotransplant which entailed left pneumonectomy,ex situ cranial lobectomy, caudal lobe reimplantation and its reperfusion for 30 min. Throughoutthe procedure, several parameters were measured in order to identify hemodynamic, gasometric andbiochemical changes. Non-parametric statistical analyses were used to compare differences between periods. Results: After ischemia, a significant increase (P < 0.05) in lipid peroxidation metabolites, proinflammatorycytokines and chemokines (TNF- , IL-1 y MCP-1), neutrophil activation, inducible nitric oxide synthaseactivity and protein-kinase MAPK p38 levels were observed in lung tissue. However, constitutive nitricoxide synthase activity in lung tissue and carbon monoxide plasma levels were decrease. The same heldtrue throughout the reperfusion period, when an increase in the constitutive heme-oxygenase activitywas also shown.Conclusions: An experimental model of normothermic lung IR injury is presented and detailed changes inhemodynamic, gasometric and biochemical parameters are shown. Both the model and the studied parametersmay be clinically useful in future investigations testing new therapies to prevent normothermicIR induced lung injury(AU)

Experimental Swine lung autotransplant model to study lung ischemia-reperfusion injury.

INTRODUCTION: Ischemia-reperfusion (IR) lung injury has been investigated extensively on clinical and experimental models of cold ischemia. However, relatively few studies examine the detailed biochemical changes occurring during normothermic (warm) IR. The objective of this work was to establish an experimental lung autotransplant model to be carried out on pigs in order to study the early stages of normothermic lung IR. ANIMALS Y METHODS: Six Large-White pigs underwent a lung autotransplant which entailed left pneumonectomy, ex situ cranial lobectomy, caudal lobe reimplantation and its reperfusion for 30 min. Throughout the procedure, several parameters were measured in order to identify hemodynamic, gasometric and biochemical changes. Non-parametric statistical analyses were used to compare differences between periods. RESULTS: After ischemia, a significant increase (P < 0.05) in lipid peroxidation metabolites, proinflammatory cytokines and chemokines (TNF-α, IL-1ß y MCP-1), neutrophil activation, inducible nitric oxide synthase activity and protein-kinase MAPK p38 levels were observed in lung tissue. However, constitutive nitric oxide synthase activity in lung tissue and carbon monoxide plasma levels were decrease. The same held true throughout the reperfusion period, when an increase in the constitutive heme-oxygenase activity was also shown. CONCLUSIONS: An experimental model of normothermic lung IR injury is presented and detailed changes in hemodynamic, gasometric and biochemical parameters are shown. Both the model and the studied parameters may be clinically useful in future investigations testing new therapies to prevent normothermic IR induced lung injury.