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1.
Ann Vasc Surg ; 83: 240-250, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34933108

RESUMEN

BACKGROUND: For surgical treatment of primary aortic infection and aortic graft infection, in situ reconstruction with autologous vein(s) has the lowest rates of re-infection and of graft thrombosis. In this study, we have assessed the outcome after autologous femoral vein reconstruction in patients with aortic (graft) infection and we provide insights into the specific technical surgical considerations of the procedure. METHODS: In this retrospective single-center study, all patients who underwent autologous femoral vein reconstruction because of primary aortic infection or aortic graft infection between January 2012 and January 2020 were included. The primary outcome parameter was 30-day mortality. RESULTS: Twenty-nine patients with autologous femoral vein reconstruction for a primary aortic infection (n = 3) or aortic graft infection (n = 26) were included. An aorto-enteral fistula was detected in 13 patients (49%). Venous reconstruction of the aorta was performed with a single femoral vein in 17 patients (59%), and two femoral veins in 12 patients (41%). Thirty-day mortality was 17%. Relapse of infection occurred in two patients (7%) and no amputations were needed. One year after surgery, only three patients (10%) still needed stockings and after 2 years none of the patients used stockings. CONCLUSIONS: Central aortic reconstruction with femoral veins is a durable solution for primary aortic and aortoiliac graft infections with a low incidence of reinfections, amputations, and venous hypertension.


Asunto(s)
Implantación de Prótesis Vascular , Infecciones Relacionadas con Prótesis , Aorta/diagnóstico por imagen , Aorta/cirugía , Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Vena Femoral/cirugía , Vena Femoral/trasplante , Humanos , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
2.
Paediatr Anaesth ; 31(11): 1150-1160, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34379843

RESUMEN

Living-donor kidney transplantation is the first choice therapy for children with end-stage renal disease and shows good long-term outcome. Etiology of renal failure, co-morbidities, and hemodynamic effects, due to donor-recipient size mismatch, differs significantly from those in adult patients. Despite the complexities related to both patient and surgery, there is a lack of evidence-based anesthesia guidelines for pediatric kidney transplantation. This educational review summarizes the pathophysiological changes to consider and suggests recommendations for perioperative anesthesia care, based on recent research papers.


Asunto(s)
Anestesia , Fallo Renal Crónico , Trasplante de Riñón , Niño , Humanos , Riñón , Donadores Vivos , Atención Perioperativa
3.
Eur J Anaesthesiol ; 36(7): 494-501, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30920983

RESUMEN

BACKGROUND: Profound neuromuscular blockade (NMB) during anaesthesia has been shown to reduce postoperative pain scores, when compared with a moderate block. We hypothesised that profound NMB during laparoscopic donor nephrectomy (LDN) could also improve the early quality of recovery after surgery. OBJECTIVES: To compare the effectiveness of profound versus moderate NMB during LDN in enhancing postoperative recovery. DESIGN: A phase IV, double-blinded, randomised controlled trial. SETTING: Multicentre trial, from November 2016 to December 2017. PATIENTS: A total of 101 living kidney donors scheduled for LDN were enrolled, and 96 patients were included in the analyses. INTERVENTIONS: Patients were randomised to receive profound (posttetanic count 1 to 3) or moderate (train-of-four count 1 to 3) neuromuscular block. MAIN OUTCOME MEASURES: The primary outcome was the early quality of recovery at postoperative day 1, measured by the Quality of Recovery-40 Questionnaire. Secondary outcomes were adverse events, postoperative pain, analgesic consumption and length-of-stay. RESULTS: The intention-to-treat analysis did not show a difference with regard to the quality of recovery, pain scores, analgesic consumption and length-of-stay. Less intra-operative adverse events occurred in patients allocated to profound NMB (1/48 versus 6/48). Five patients allocated to a profound NMB received a moderate block and in two patients neuromuscular monitoring failed. The as-treated analysis revealed that pain scores were significantly lower at 6, 24 and 48 h after surgery. Moreover, the quality of recovery was significantly better at postoperative day 2 in patients receiving a profound versus moderate block (179.5 ±â€Š13.6 versus 172.3 ±â€Š19.2). CONCLUSION: Secondary analysis indicates that an adequately maintained profound neuromuscular block improves postoperative pain scores and quality of recovery. As the intention-to-treat analysis did not reveal a difference regarding the primary endpoint, future studies should pursue whether a thoroughly maintained profound NMB during laparoscopy improves relevant patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838134.


Asunto(s)
Laparoscopía/métodos , Nefrectomía/métodos , Bloqueo Neuromuscular/métodos , Recolección de Tejidos y Órganos/métodos , Anciano , Método Doble Ciego , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Monitoreo Neuromuscular/métodos , Dolor Postoperatorio/epidemiología , Periodo Posoperatorio
4.
World J Surg ; 41(11): 2950-2958, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28608013

RESUMEN

BACKGROUND: The use of low intra-abdominal pressure (<10 mmHg) reduces postoperative pain scores after laparoscopic surgery. OBJECTIVE: To investigate whether low-pressure pneumoperitoneum with deep neuromuscular blockade improves the quality of recovery after laparoscopic donor nephrectomy (LDN). DESIGN, SETTING AND PARTICIPANTS: In a single-center randomized controlled trial, 64 live kidney donors were randomly assigned to 6 or 12 mmHg insufflation pressure. A deep neuromuscular block was used in both groups. Surgical conditions were rated by the five-point Leiden-surgical rating scale (L-SRS), ranging from 5 (optimal) to 1 (extremely poor) conditions. If the L-SRS was insufficient, the pressure was increased stepwise. MAIN OUTCOME MEASURE: The primary outcome measure was the overall score on the quality of recovery-40 (QOR-40) questionnaire at postoperative day 1. RESULTS: The difference in the QOR-40 scores on day 1 between the low- and standard-pressure group was not significant (p = .06). Also the overall pain scores and analgesic consumption did not differ. Eight procedures (24%), initially started with low pressure, were converted to a standard pressure (≥10 mmHg). A L-SRS score of 5 was significantly more prevalent in the standard pressure as compared to the low-pressure group at 30 min after insufflation (p < .01). CONCLUSIONS: Low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade during LDN does not reduce postoperative pain scores nor improve the quality of recovery in the early postoperative phase. The question whether the use of deep neuromuscular blockade during laparoscopic surgery reduces postoperative pain scores independent of the intra-abdominal pressure should be pursued in future studies. TRIAL REGISTRATION: The trial was registered at clinicaltrial.gov before the start of the trial (NCT02146417).


Asunto(s)
Laparoscopía/métodos , Nefrectomía/métodos , Bloqueo Neuromuscular/métodos , Neumoperitoneo Artificial , Recolección de Tejidos y Órganos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Presión , Encuestas y Cuestionarios
5.
World J Urol ; 34(7): 955-61, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26369548

RESUMEN

PURPOSE: To minimize cold ischemia time, transplantations with kidneys from deceased donors are frequently performed during the night. However, sleep deprivation of those who perform the transplantation may have adverse effects on cognitive and psychomotor performance and may cause reduced cognitive flexibility. We hypothesize that renal transplantations performed during the night are associated with an increased incidence of pure technical graft failure. METHODS: A retrospective analysis of data of the Dutch Organ Transplant Registry concerning all transplants from deceased donors between 2000 and 2013 was performed. Nighttime surgery was defined as the start of the procedure between 8 p.m. and 8 a.m. The primary outcome measure was technical graft failure, defined as graft loss within 10 days after surgery without signs of (hyper)acute rejection. RESULTS: Of 4.519 renal transplantations in adult recipients, 1.480 were performed during the night. The incidence of pure technical graft failure was 1.0 % for procedures started during the night versus 2.6 % for daytime surgery (p = .001). In a multivariable model, correcting for relevant donor, recipient and graft factors, daytime surgery was an independent predictor of pure technical graft failure (p < .001). CONCLUSIONS: Limitation of this study is mainly to its retrospective design, and the influence of some relevant variables, such as the experience level of the surgeon, could not be assessed. We conclude that nighttime surgery is associated with less pure technical graft failures. Further research is required to explore factors that may positively influence the performance of the surgical team during the night.


Asunto(s)
Atención Posterior/normas , Rechazo de Injerto/etiología , Trasplante de Riñón/métodos , Complicaciones Posoperatorias/etiología , Femenino , Rechazo de Injerto/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del Tratamiento
6.
World J Surg ; 40(2): 471-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26319261

RESUMEN

BACKGROUND: The lengths of right renal veins are shorter when compared to their left counterparts. Since the implantation of kidneys with short renal veins is considered more challenging, many surgeons prefer left kidneys for transplantation. Therefore, our hypothesis is that the implantation of right kidneys from living and deceased donors is associated with more technical graft failures as compared to left kidneys. METHODS: Two consecutive cohorts of adult renal allograft recipients of living (n = 4.372) and deceased (n = 5.346) donor kidneys between January 1, 2000 and January 1, 2013 were analyzed. Data were obtained from the prospectively maintained electronic database of the Dutch Organ Transplant Registry. Technical graft failure was defined as failure of the renal allograft within 10 days after renal transplantation without signs of acute rejection. RESULTS: In the living donor kidney transplantation cohort, the implantation of right donor kidneys was associated with a higher incidence of technical graft failure (multivariate analysis p = 0.03). For recipients of deceased donor kidneys, the implantation of right kidneys was not significantly associated with technique-related graft failure (multivariate analysis p = 0.16). CONCLUSIONS: Our data show that the implantation of right kidneys from living donors is associated with a higher incidence of technique-related graft failure as compared to left kidneys.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón/métodos , Riñón/cirugía , Venas Renales/anatomía & histología , Sitio Donante de Trasplante/anatomía & histología , Adulto , Femenino , Humanos , Riñón/irrigación sanguínea , Trasplante de Riñón/efectos adversos , Donadores Vivos , Masculino , Persona de Mediana Edad , Países Bajos , Tamaño de los Órganos , Sistema de Registros
7.
World J Urol ; 33(5): 733-41, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25362559

RESUMEN

PURPOSE: Limited evidence exists that optimization of surgical team composition may improve effectiveness of laparoscopic donor nephrectomy (LDN). METHODS: A retrospective cohort study with 541 consecutive LDNs. From 2003 to 2012, surgical team composition was gradually optimized with regard to the surgeons' experience, proficient assistance and the use of fixed teams. RESULTS: Multivariable analysis showed that a surgical team with an experienced surgeon had a significantly shorter operation time (OT) (-18 min, 95% CI -28 to -9), less estimated blood loss (EBL) (-64 mL, 95% CI -108 to -19) and shorter length of stay (LOS) (-1 day, 95% CI -1.6 to 0). Proficient assistance was also independently associated with a shorter OT (-43 min, 95% CI -53 to -33) and reduced EBL (-58 mL, 95% CI -109 to -6), whereas those procedures performed by fixed teams were related to a shorter operation (-50 min, 95% CI -59 to -43) and warm ischemia time (-1.8, 95% CI -2.1 to -1.5), a reduced mean complication grade (-0.14 per patient, 95% CI -0.3 to -0.02) and a shorter LOS (-1.1 day, 95% CI -1.7 to -05). Health care costs for LDN by one staff surgeon with unproficient assistance were 7.707 Euro, whereas costs for LDN by two staff surgeons in fixed teams were 5.614 Euro. CONCLUSIONS: Surgical team composition has a major impact on variables that reflect the effectiveness of LDN from the donors' perspective. Health care costs are lower for LDNs performed by two experienced surgeons in fixed team composition. We advocate the use of two experienced surgeons in fixed team composition for LDN.


Asunto(s)
Costos de la Atención en Salud/estadística & datos numéricos , Trasplante de Riñón/economía , Laringoscopía/economía , Donadores Vivos , Cuerpo Médico/normas , Nefrectomía/economía , Competencia Profesional/normas , Adulto , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Estudios de Cohortes , Análisis Costo-Beneficio , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos , Tempo Operativo , Estudios Retrospectivos , Resultado del Tratamiento
8.
Ann Vasc Surg ; 29(6): 1188-95, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26009479

RESUMEN

BACKGROUND: The objective of our study was to analyze the efficacy of autologous superficial femoropopliteal vein reconstruction for primary aortic or aortic graft infection. METHODS: We performed a retrospective analysis of 14 patients treated for an infected aortic prosthesis or primary infected aorta between 2012 and 2014. Three patients had a primary mycotic aneurysm caused by a Salmonella or Coxiella burnetti infection. Seven patients were treated previously for aortic aneurysms with a conventional Dacron vascular prosthesis and 4 with an endovascular prosthesis. All infected prostheses were explanted via median laparotomy with subsequent debridement of the aortic aneurysm wall. Aortic reconstruction was performed with 1 or 2 superficial femoropopliteal veins, interpositioning the greater omentum when possible. The primary outcome measure was 30-day mortality. Secondary outcome measures were reoperation, operating time, amputation rate, length of intensive care unit (ICU) and hospital stay, reinfection rate, and limb edema requiring compression therapy. RESULTS: The 30-day mortality was 28%. Two patients died of an abdominal sepsis, one patient of a cerebrovascular accident and another of a hypovolemic shock. One patient died at home 2 years after surgery of unknown cause. Four patients required a reoperation. The median intraoperative blood loss was 1,500 mL (500-8000). Median operating time was 364 min (264-524). Median length of ICU stay was 3.5 days (1-47), and median hospital stay was 20 days (10-47). There were no limb amputations. Mild edema of the donor leg was documented in 2 patients. Compression stockings were not worn by any patients. Postoperative antibiotic treatment was administered for at least 6 weeks. No recurrent infections were diagnosed. CONCLUSIONS: Autologous venous reconstruction of the aorta offers advantages over other therapeutic approaches and deserves a prominent place in the treatment of the primary infected aorta or an infected aortic prosthetic graft.


Asunto(s)
Aneurisma Infectado/cirugía , Aneurisma de la Aorta/cirugía , Prótesis Vascular/efectos adversos , Vena Femoral/trasplante , Procedimientos de Cirugía Plástica , Vena Poplítea/trasplante , Infecciones Relacionadas con Prótesis/cirugía , Fiebre Q/cirugía , Infecciones por Salmonella/cirugía , Anciano , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/microbiología , Aneurisma Infectado/mortalidad , Antibacterianos/uso terapéutico , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/microbiología , Aneurisma de la Aorta/mortalidad , Aortografía/métodos , Autoinjertos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/mortalidad , Fiebre Q/diagnóstico , Fiebre Q/microbiología , Fiebre Q/mortalidad , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/mortalidad , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Infecciones por Salmonella/diagnóstico , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/mortalidad , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
10.
J Surg Oncol ; 101(3): 259-69, 2010 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-20039272

RESUMEN

Metalloproteinases (MPs) such as the matrix metalloproteinases (MMPs) and adamalysins (ADAMs and ADAMTS) are expressed in various stages of colorectal cancer (CRC), and some correlate with survival and prognosis. The MPs are regulated by various factors including EMMPRIN, TIMPs, and RECK. In addition, micro-RNAs are found to be relevant for both MP expression levels and CRC prognostication. Both MPs and their regulators could be potential targets for intervention and therapy in CRC.


Asunto(s)
Neoplasias Colorrectales/enzimología , Metaloproteasas/fisiología , Neoplasias Colorrectales/etiología , Activación Enzimática , Proteínas Ligadas a GPI , Humanos , Glicoproteínas de Membrana/fisiología , Metaloendopeptidasas/fisiología , Metaloproteasas/genética , MicroARNs/fisiología , Inhibidores Tisulares de Metaloproteinasas/fisiología
11.
Transplant Direct ; 5(12): e509, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32095504

RESUMEN

BACKGROUND: In most western countries, the median donor age is increasing. The incidence of malignancies in older populations is increasing as well. To prevent donor-derived malignancies we evaluated radiologic donor screening in a retrospective donor cohort. METHODS: This study analyzes the efficacy of a preoperative computed tomography (CT) scan on detecting malignancies. All deceased organ donors in the Netherlands between January 2013 and December 2017 were included. Donor reports were analyzed to identify malignancies detected before or during organ procurement. Findings between donor screening with or without CT-scan were compared. RESULTS: Chest or abdominal CT-scans were performed in 17% and 18% of the 1644 reported donors respectively. Screening by chest CT-scan versus radiograph resulted in 1.5% and 0.0% detected thoracic malignancies respectively. During procurement no thoracic malignancies were found in patients screened by chest CT compared with 0.2% malignancies in the radiograph group. Screening by abdominal CT-scan resulted in 0.0% malignancies, compared with 0.2% in the abdominal ultrasound group. During procurement 1.0% and 1.3% malignancies were found in the abdominal CT-scan and ultrasound groups, respectively. CONCLUSIONS: Screening by CT-scan decreased the perioperative detection of tumors by 30%. A preoperative CT-scan may be helpful by providing additional information on (aberrant) anatomy to the procuring or transplanting surgeon. In conclusion, donor screening by CT-scan could decrease the risk of donor-derived malignancies and prevents unnecessary procurements per year in the Netherlands.

12.
J Endourol ; 32(1): 54-58, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29186976

RESUMEN

BACKGROUND: Laparoscopic surgery may be complicated by visual disturbances, including lens fogging. Several techniques have been developed to prevent laparoscopic lens fogging (LLF). We aim to compare the effectiveness of two commonly available techniques in prevention of LLF: heated sterile water in a thermos flask and ResoClear® impregnation wipes. MATERIALS AND METHODS: In this single-center prospective randomized study, 50 patients underwent an elective laparoscopic donor nephrectomy and were allocated to either heated sterile water or ResoClear® impregnation wipes as the antifogging method. The primary outcome was the number of fogging events during the first 30 minutes of the operation, whereas secondary outcomes were operating time, number of cleaning events because of other causes, cost differences, and assessment of predicting factors for fogging events. RESULTS: In 50 patients, the outcomes were analyzed. The number of fogging events was significantly lower when using heated sterile water (median = 0, interquartile range [IQR]: 0-0) compared to ResoClear® (median 1.0, IQR: 0.5-3.0), p < 0.001. There were no significant differences in operating time, number of cleaning events because of other causes, and costs. No predictors of fogging events were found. CONCLUSION: The use of heated sterile water leads to significantly less fogging events than the use of ResoClear® impregnation wipes, resulting in an improved continuity of the surgery without differences in operating time and costs.


Asunto(s)
Calor , Laparoscopios , Laparoscopía/métodos , Lentes , Tensoactivos , Agua , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Prospectivos
13.
Cancer Lett ; 237(2): 289-97, 2006 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-16046057

RESUMEN

mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R(s)=0.6-0.8, P<0.001). For active MMP-2, but not for MMP-9, a significant negative partial correlation (R(p)=-0.440, P<0.001) for RECK was found in tumor tissue, which was confirmed by linear regression analysis. In exploratory survival analyses we found that in patients with localized disease the RECK level in normal or tumor tissue had a significant (P=0.017) association with overall survival.


Asunto(s)
Basigina/biosíntesis , Neoplasias Colorrectales/enzimología , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Glicoproteínas de Membrana/biosíntesis , Supervivencia Celular , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Femenino , Proteínas Ligadas a GPI , Predisposición Genética a la Enfermedad , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Pronóstico , ARN Mensajero/metabolismo , Factores de Tiempo , Resultado del Tratamiento
15.
Ann Transplant ; 20: 532-8, 2015 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-26356283

RESUMEN

BACKGROUND Implantation of a kidney with a short renal vein is technically more challenging and therefore prone for technique-related complications. It remains unclear whether pre-operative computed tomography angiography (CTA), to assess vascular anatomy of the donor kidney, can be used to predict renal vein length. MATERIAL AND METHODS Right and left renal vein lengths of 100 consecutive kidney donors were measured in an oblique-coronal plane multiplanar reconstruction image of 100 consecutive kidney donors in whom ex vivo vein length was measured after recovery. In a second retrospective cohort of 100 consecutive kidney donors donating a right kidney, preoperative CTA vein length measurements were correlated to anastomosis time and early graft outcome. RESULTS Left and right renal vein lengths, measured on CTA, were 43.2 mm and 30.0 mm, respectively. No correlation was found between CTA and ex vivo measurements for the left renal vein (p=.610), whereas a significant correlation was found for the right renal vein (p=.021). In the retrospective cohort, right renal vein length was significantly correlated with the anastomosis time but not with early graft outcome. CONCLUSIONS The length of the right, but not the left, renal vein can be predicted by preoperative CTA, but this does not hold true for the left renal vein.


Asunto(s)
Trasplante de Riñón/métodos , Riñón/diagnóstico por imagen , Nefrectomía/métodos , Venas Renales/diagnóstico por imagen , Adulto , Anciano , Angiografía , Femenino , Humanos , Riñón/cirugía , Laparoscopía , Donadores Vivos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Venas Renales/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
17.
Crit Care Med ; 30(7): 1553-9, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12130978

RESUMEN

OBJECTIVE: To examine the role of inducible nitric oxide synthase (iNOS) in the development of the multiple organ dysfunction syndrome (MODS) in a murine model by using either a selective iNOS inhibitor or iNOS knockout mice. DESIGN: Prospective randomized laboratory study. SETTING: Central animal laboratory and experimental laboratory. SUBJECTS: Fifty inbred C57BL/6 mice, 39 iNOS knockout (-/-) mice, and 30 wild-type (+/+) mice, 7-9 wks old, weighing 20-25 g. INTERVENTIONS: Mice received an aseptic intraperitoneal injection of 40 microg of lipopolysaccharide followed by zymosan at a dose of 1 mg/g of body weight 6 days later (day 0). In experiment 1, C57BL/6 mice additionally received intraperitoneal injections with 5 mg of aminoguanidine or saline every 12 hrs, from 4 days after the injection of zymosan onward. In experiment 2, both iNOS-/- mice and corresponding wild-type (iNOS+/+) mice were treated with lipopolysaccharide and zymosan. MEASUREMENTS AND MAIN RESULTS: In all animals, the injection of zymosan induced an acute peritonitis, followed by an apparent recovery. From approximately day 6 onward, animals entered the third-MODS-like-phase, indicated by weight loss, a decrease in body temperature, and significant mortality rates. Quantitative reverse transcriptase polymerase chain reaction and immunochemistry revealed a strongly increased expression of iNOS messenger RNA and iNOS protein in livers of mice in the last phase. However, neither the in vivo administration of aminoguanidine to C57BL/6 mice nor the complete absence of iNOS enzyme (iNOS-/- mice) had a beneficial effect on survival rate, body temperature, or body weight. In addition, relative lung, liver, and spleen weights and lung scores were not different between experimental groups. CONCLUSIONS: The current results strongly argue against an essential and causative role of iNOS in the development of organ damage in our murine model of MODS.


Asunto(s)
Insuficiencia Multiorgánica/enzimología , Óxido Nítrico Sintasa/fisiología , Animales , Guanidinas/farmacología , Ratones , Ratones Endogámicos C57BL , Insuficiencia Multiorgánica/inducido químicamente , Óxido Nítrico Sintasa/antagonistas & inhibidores , Distribución Aleatoria , Zimosan/administración & dosificación
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