Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
Semin Vasc Surg ; 14(4): 255-65, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11740833

RESUMEN

Ischemia of the colon, rectum, and pelvis continues to be a significant source of morbidity and mortality after aortic reconstruction. Complications associated with colonic and pelvic ischemia are severe and include impotency, buttock claudication, colonic and rectal infarction, buttock and perineal necrosis, and spinal cord or lumbar plexus injury. To prevent these complications the vascular surgeon must make every attempt to guarantee the adequacy of colonic and pelvic blood supply after aortic reconstructive procedures. During open surgical repair of aneurysms or aortoiliac arterial occlusive disease, patent inferior mesenteric arteries must either be routinely reimplanted or selectively ligated on the basis of object intraoperative assessment of colonic perfusion. In addition, when possible, antegrade perfusion should be maintained in patent internal iliac arteries, and femoral reconstructions should include reconstruction of the deep femoral artery to assure adequate perfusion of potential pelvic collaterals. The rate of colonic and pelvic ischemia after endovascular aneurysm repair appears lower than after open repair, but all of the complications of colonic and pelvic ischemic seen after open repairs have been reported after endoluminal aneurysm repair. Thus, during stent-graft repair of abdominal aortic aneurysms, all attempts also should be made to preserve pelvic perfusion by maintaining antegrade flow to a least one patent internal iliac artery. The principle to remember in the management of complications of pelvic ischemia associated with aortic reconstruction is prevention because when complications of pelvic ischemia occur, the damage often is irreversible.


Asunto(s)
Aorta/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/complicaciones , Rotura de la Aorta/cirugía , Colon Sigmoide/irrigación sanguínea , Isquemia/etiología , Isquemia/terapia , Pelvis/irrigación sanguínea , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Vasculares , Circulación Colateral/fisiología , Humanos , Incidencia , Plexo Lumbosacro/irrigación sanguínea , Complicaciones Posoperatorias/terapia , Médula Espinal/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares/efectos adversos
2.
Radiat Res ; 156(1): 53-60, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11418073

RESUMEN

Rectenwald, J. E., Pretus, H. A., Seeger, J. M., Huber, T. S., Mendenhall, N. P., Zlotecki, R. A., Palta, J. R., Li, Z. F., Hook, S. Y., Sarac, T. P., Welborn, M. B., Klingman, N. V., Abouhamze, Z. S. and Ozaki, C. K. External-Beam Radiation Therapy for Improved Dialysis Access Patency: Feasibility and Early Safety. Radiat. Res. 156, 53-60 (2001).Prosthetic dialysis access grafts fail secondary to neointimal hyperplasia at the venous anastomosis. We hypothesized that postoperative single-fraction external-beam radiation therapy to the venous anastomosis of hemodialysis grafts can be used safely in an effort to improve access patency. Dogs (n = 8) underwent placement of expanded polytetrafluoroethylene grafts from the right carotid artery to the left jugular vein. Five dogs received single-fraction external-beam photon irradiation (8 Gy) to the venous anastomosis after surgery. Controls were not irradiated. Shunt angiograms were completed 3 and 6 months postoperatively. Anastomoses, mid-graft, and the surrounding tissues were analyzed. Immunohistochemistry for smooth muscle cell alpha-actin, proliferating cellular nuclear antigen (PCNA), and apoptosis was performed. Incisions healed well, though all animals developed wound seromas. One control suffered graft thrombosis 4 months postoperatively. Angiography/histology confirmed severe neointimal hyperplasia at the venous anastomosis. The remaining seven dogs developed similar amounts of neointimal hyperplasia. PCNA studies showed no accelerated fibroproliferative response at irradiated anastomoses compared to controls. Skin incisions and soft tissues over irradiated anastomoses revealed no radiation-induced changes or increase in apoptosis. Thus we conclude that postoperative single-fraction external-beam irradiation of the venous anastomosis of a prosthetic arteriovenous graft that mimics the situation in humans is feasible and safe with regard to early wound healing.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Prótesis Vascular , Oclusión de Injerto Vascular/prevención & control , Túnica Íntima/efectos de la radiación , Grado de Desobstrucción Vascular/efectos de la radiación , Actinas/metabolismo , Animales , Apoptosis/efectos de la radiación , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/instrumentación , Prótesis Vascular/efectos adversos , Arterias Carótidas/metabolismo , Arterias Carótidas/efectos de la radiación , Perros , Estudios de Factibilidad , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/patología , Inmunohistoquímica , Venas Yugulares/metabolismo , Venas Yugulares/efectos de la radiación , Politetrafluoroetileno , Antígeno Nuclear de Célula en Proliferación/metabolismo , Diálisis Renal/métodos , Piel/efectos de la radiación , Túnica Íntima/metabolismo , Túnica Íntima/patología , Cicatrización de Heridas/efectos de la radiación
3.
Crit Care Med ; 28(9): 3191-7, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11008981

RESUMEN

OBJECTIVES: Plasma proinflammatory, anti-inflammatory cytokine, and soluble tumor necrosis factor (TNF) receptor concentrations were examined in hospitalized patients after abdominal and thoracoabdominal aortic aneurysm (TAAA) repair, with and without left atrial femoral bypass. Changes in plasma cytokine concentrations were related to the duration of visceral ischemia and the frequency rate of postoperative, single, or multiple system organ dysfunction (MSOD). DESIGN: Prospective, observational study. SETTING: Two academic referral centers in the United States and The Netherlands. PATIENTS: We included 16 patients undergoing TAAA repair without left atrial femoral bypass, 12 patients undergoing TAAA repair with left atrial femoral bypass, and nine patients undergoing infrarenal aortic aneurysm repair. MEASUREMENTS AND MAIN RESULTS: Timed, arterial blood sampling for proinflammatory and anti-inflammatory cytokine and soluble TNF receptor concentrations (p55 and p75), and prospective assessment of postoperative single and MSOD. Plasma appearance of TNF-alpha, interleukin (IL)-6, IL-8, and IL-10 peaked 1 to 4 hrs after TAAA repair, and concentrations were significantly elevated compared with infrarenal abdominal aortic aneurysm repair (p < .05). Left atrial femoral bypass significantly reduced the duration of visceral ischemia (p < .05) and the systemic TNF-alpha, p75, and IL-10 responses (p < .05). Plasma TNF-alpha concentrations >150 pg/mL were more common in patients with extended visceral ischemia times (>40 mins). Additionally, patients with early peak TNF-alpha concentrations >150 pg/mL and IL-6 levels >1,000 pg/mL developed MSOD more frequently than patients without these elevated plasma cytokine levels (both p < .05). CONCLUSIONS: Thoracoabdominal aortic aneurysm repair results in the increased plasma appearance of TNF-alpha, IL-6, IL-8, IL-10, and shed TNF receptors. The frequency and magnitude of postoperative organ dysfunction after TAAA repair is associated with an increased concentration of the cytokines, TNF-alpha, and IL-6 and the increased plasma levels of these cytokines appear to require extended visceral ischemia times.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Citocinas/sangre , Isquemia/inmunología , Complicaciones Posoperatorias/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Vísceras/irrigación sanguínea , Anciano , Femenino , Humanos , Isquemia/diagnóstico , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/inmunología , Complicaciones Posoperatorias/diagnóstico , Pronóstico , Estudios Prospectivos , Receptores del Factor de Necrosis Tumoral/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico
4.
J Vasc Surg ; 32(3): 451-9; discussion 460-1, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10957651

RESUMEN

OBJECTIVE: The purpose of this study was to determine long-term outcome in patients with infected prosthetic aortic grafts who were treated with extra-anatomic bypass grafting and aortic graft removal. METHODS: Between January 1989 and July 1999, 36 patients were treated for aortic graft infection with extra-anatomic bypass grafting and aortic graft removal. Extra-anatomic bypass graft types were axillofemoral femoral (5), axillofemoral (26; bilateral in 20), axillopopliteal (3; bilateral in 1) and axillofemoral/axillopopliteal (2). The mean follow-up was 32.3 +/- 4. 8 months. RESULTS: Four patients (11%) died in the postoperative period, and two patients died during follow-up as a direct consequence of extra-anatomic bypass grafting and aortic graft removal (one died 7 months after extra-anatomic bypass graft failure, one died 36 months after aortic stump disruption). One additional patient died 72 months after failure of a subsequent aortic reconstruction, so that the overall treatment-related mortality was 19%, whereas overall survival by means of life table analysis was 56% at 5 years. No amputations were required in the postoperative period, but four patients (11%) required amputation during follow-up. Twelve patients (35%) had extra-anatomic bypass graft failure during follow-up, and six patients underwent secondary aortic reconstruction (thoracobifemoral [2], iliofemoral [2], femorofemoral [2]). However, with the exclusion of patients undergoing axillopopliteal grafts (primary patency 0% at 7 months), only seven patients (25%) had extra-anatomic bypass graft failure, and only two patients required amputation (one after extra-anatomic bypass graft removal for infection, one after failure of a secondary aortic reconstruction). Furthermore, primary and secondary patency rates by means of life table analysis were 75% and 100% at 41 months for axillofemoral femoral grafts and 64% and 100% at 60 months for axillofemoral grafts. Only one patient required extra-anatomic bypass graft removal for recurrent infection, and only one late aortic stump disruption occurred. CONCLUSIONS: Staged extra-anatomic bypass grafting (with axillofemoral bypass graft) and aortic graft removal for treatment of aortic graft infection are associated with acceptable early and long-term outcomes and should remain a primary approach in selected patients with this grave problem.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Enfermedades de la Aorta/cirugía , Arteriopatías Oclusivas/cirugía , Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Remoción de Dispositivos , Infecciones Relacionadas con Prótesis/cirugía , Anciano , Arteria Axilar/cirugía , Arteria Femoral/cirugía , Estudios de Seguimiento , Humanos , Arteria Ilíaca/cirugía , Persona de Mediana Edad , Reoperación
5.
Shock ; 14(2): 157-62, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10947160

RESUMEN

Multiple organ dysfunction and death are common sequelae after mesenteric ischemia-reperfusion injury as seen with mesenteric revascularization and thoracoabdominal aortic aneurysm repair. A second insult such as bacterial pneumonia occurring subsequent to the ischemia-reperfusion injury may contribute to these untoward effects. We hypothesized the sequential visceral/lower torso ischemia-reperfusion and endotoxemia in a murine model would increase the magnitude of the proinflammatory cytokine response and decrease survival. C57BL/6 mice underwent 20 min of supraceliac occlusion (IR), sham laparotomy (LAP), or no initial insult (CTRL) followed by intraperitoneal injection of a lethal dose of endotoxin (LPS [lipopolysaccharide 50 mg/kg] or saline vehicle at 24 h. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (IL-10, IL-6) or WEHI bioassay [tumor necrosis factor (TNF)], and survival was determined at 5 days. The role of IL-10 on the TNF response and survival was examined in a subset of mice given mouse anti IL-10 IgM (25 mg/kg intraperitoneally) 2 h prior to the initial insult. Survival after LPS was significantly different (P < 0.05) among the treatment groups (IR, 64%; LAP, 55%; CTRL, 11%) and appeared to trend directly with the magnitude of the initial operation. The serum IL-10 levels in the IR and LAP groups were significantly increased 4 h after the initial insult and remained elevated at 24 h. Peak serum TNF levels after LPS were significantly lower in the IR and LAP groups. Administration of anti IL-10 IgM resulted in uniform mortality and a significant increase in the peak TNF levels after LPS administration for all initial treatment groups. Endogenous production of IL-10 following laparotomy down-regulates the TNF response and improves survival after endotoxemia.


Asunto(s)
Endotoxemia/prevención & control , Interleucina-10/fisiología , Isquemia/complicaciones , Laparotomía , Insuficiencia Multiorgánica/etiología , Daño por Reperfusión/complicaciones , Vísceras/irrigación sanguínea , Animales , Aorta Torácica , Enfermedades de la Aorta/complicaciones , Constricción , Endotoxemia/complicaciones , Femenino , Inmunoglobulina M/uso terapéutico , Interleucina-10/antagonistas & inhibidores , Interleucina-10/sangre , Interleucina-10/inmunología , Mesenterio/irrigación sanguínea , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Insuficiencia Multiorgánica/prevención & control , Distribución Aleatoria , Factor de Necrosis Tumoral alfa/metabolismo
6.
Shock ; 13(6): 425-34, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10847628

RESUMEN

The results of recent anticytokine trials for sepsis syndrome have been disappointing. Several Phase II and Phase III clinical trials have shown a modest benefit in various subsets of patients; however, there has been no reported benefit in the primary endpoint of 28-day all-cause mortality. The failure of these trials is clearly multifactorial, and causes include the overall complexity of the inflammatory response, heterogeneity of the patient populations, absence of a hypercytokine response at the time of drug treatment, and the relatively short half-life of the administered drugs. The failure of anticytokine therapies may represent inadequate application of the treatment modality rather than any inherent weakness of the treatment itself. We have recently initiated a Phase I clinical trial examining the role of the anti-inflammatory cytokine IL-10 during surgical repair of a thoracoabdominal aortic aneurysm. This study may overcome some of the-design limitations of previous anticytokine trials in sepsis, and serve as a paradigm for future anticytokine therapy trials. Although the incidence of thoracoabdominal aortic aneurysms is relatively low, the patient population is homogeneous and the surgical injury associated with its repair reproducible. Additionally, postoperative mortality and morbidity rates are significant. Most importantly, the operative repair is associated with an obligatory visceral ischemia and reperfusion injury that appears to be associated with a proinflammatory cytokine response and postoperative organ dysfunction. IL-10 is a pleuripotent anti-inflammatory cytokine that both inhibits TNFalpha and IL-1 synthesis, and antagonizes their actions through upregulation of cytokine antagonists. Furthermore, IL-10 administration has been associated with only minimal adverse side effects during Phase I and Phase II trials.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Citocinas/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , Interleucina-10/uso terapéutico , Isquemia/patología , Daño por Reperfusión/patología , Vísceras/irrigación sanguínea , Animales , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Citocinas/fisiología , Evaluación Preclínica de Medicamentos , Humanos , Interleucina-1/antagonistas & inhibidores , Interleucina-10/fisiología , Metaanálisis como Asunto , Ratones , Insuficiencia Multiorgánica/etiología , Complicaciones Posoperatorias/tratamiento farmacológico , Primates , Estudios Prospectivos , Roedores , Análisis de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Insuficiencia del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
7.
J Vasc Surg ; 29(2): 370-6, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9950995

RESUMEN

PURPOSE: Tumor necrosis factor alpha (TNF-alpha) has been shown to play a role in pulmonary injury after lower-extremity ischemia/reperfusion (I/R). However, its role in direct skeletal muscle injury is poorly understood. The hypothesis that endogenous TNF production contributes to skeletal muscle injury after hindlimb I/R in rats was tested. METHODS: Juvenile male Sprague-Dawley rats underwent 4 hours of bilateral hindlimb ischemia and 4 hours of reperfusion (IR) or sham operation (SHAM). A subset was treated with a soluble TNF receptor I construct (STNFRI, 10 mg/kg) 1 hour before ischemia (PRE) or at reperfusion (POST). Direct skeletal muscle injury (SMII) and muscle endothelial capillary permeability (MPI) were quantified by means of Tc99 pyrophosphate and I125 albumin uptake. Pulmonary neutrophil infiltration and hepatocellular injury were assessed by means of myeloperoxidase content (MPO) and aspartate aminotransferase (AST) concentrations, respectively. Serum TNF bioactivity was measured with the WEHI bioassay. RESULTS: Hindlimb I/R (IR vs SHAM) resulted in a significant (P <.05) increase in the SMII (0.52 +/- 0.06 vs 0.07 +/- 0.01) and MPI (0.35 +/-.04 vs 0.06 +/- 0.01). Pretreatment with STNFRI (PRE vs IR) significantly ameliorated both SMII (0.30 +/- 0.05 vs 0.52 +/- 0.06) and MPI (0.23 +/- 0.02 vs 0.35 +/- 0.04), whereas treatment at reperfusion (POST vs IR) had no effect. Hindlimb I/R (IR vs SHAM) resulted in both significant pulmonary neutrophil infiltration (MPO 16.4 +/- 1.06 U/g vs 11.3 +/- 1.4 U/g) and hepatocellular injury (AST 286 +/- 45 U/mL vs 108 +/- 30 U/mL), but neither was inhibited by pretreatment with STNFRI before ischemia. Detectable levels of TNF were measured during ischemia in a significantly higher percentage of the IR group compared with SHAM (9 of 12 vs 3 of 12), and the maximal TNF values were also significantly greater (51.1 +/- 12.6 pg/mL vs 5.5 +/- 2.9 pg/mL). No TNF was detected in any treatment group during reperfusion nor after administration of the STNFRI. CONCLUSION: Acute hindlimb IR initiates a systemic TNF response during the ischemic period that is partly responsible for the associated skeletal muscle injury.


Asunto(s)
Músculo Esquelético/irrigación sanguínea , Daño por Reperfusión/fisiopatología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Aspartato Aminotransferasas/sangre , Permeabilidad Capilar , Miembro Posterior , Hígado/patología , Pulmón/enzimología , Pulmón/patología , Masculino , Músculo Esquelético/patología , Neutrófilos/patología , Peroxidasa/análisis , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Factor de Necrosis Tumoral alfa/análisis
8.
J Vasc Surg ; 26(1): 113-8, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9240329

RESUMEN

INTRODUCTION: Visceral ischemia and reperfusion associated with thoracoabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory cytokines. The purpose of this study was to determine the effect of exogenous administration of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine production (IL-6 and TNF alpha) and pulmonary neutrophil infiltration after acute visceral ischemia-reperfusion. METHODS: Two hours before 25 minutes of supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 microgram [n = 20], 2 micrograms [n = 20], 5 micrograms [n = 25], or 20 micrograms [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 micrograms. Twenty-five additional mice underwent visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent laparotomy without aortic occlusion (sham). RESULTS: Pretreatment with exogenous rhIL-10 resulted in significant reductions in lung neutrophil infiltration with 0.2 microgram, 2 micrograms, and 5 micrograms per mouse of rhIL-10 compared with lung neutrophil levels in control mice that underwent acute visceral ischemia-reperfusion alone (p < 0.05). In addition, serum TNF alpha was detected in 50% of control mice and in 75% of mice that received murine anti-IL-10, but in none of the mice that received rhIL-10 (2 micrograms per mouse) or the mice that underwent sham operative procedures (p < 0.05 by chi 2 analysis). CONCLUSION: Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNF alpha in this model of visceral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may offer a novel therapeutic approach to decrease the complications that are associated with TAAA repair.


Asunto(s)
Interleucina-10/farmacología , Pulmón/patología , Neutrófilos/patología , Daño por Reperfusión/patología , Vísceras/irrigación sanguínea , Enfermedad Aguda , Animales , Aorta/fisiología , Movimiento Celular , Constricción , Femenino , Inmunoglobulina M/administración & dosificación , Interleucina-10/inmunología , Interleucina-6/sangre , Pulmón/enzimología , Ratones , Ratones Endogámicos C57BL , Neutrófilos/fisiología , Peroxidasa/metabolismo , Proteínas Recombinantes/farmacología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Factor de Necrosis Tumoral alfa/análisis
9.
J Surg Res ; 69(2): 425-8, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9224418

RESUMEN

Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (I/R). The anti-inflammatory cytokine interleukin-10 (IL-10) inhibits both TNF-alpha and IL-1, and we hypothesized that exogenous human IL-10 may decrease lung and soleus muscle injury after hindlimb I/R. Male Sprague-Dawley rats were randomly assigned to I/R (n = 10); I/R+IL-10 (10 micrograms i.v., n = 10), SHAM (n = 4); or SHAM+IL-10 (10 micrograms i.v., n = 4). Bilateral hindlimb ischemia was produced by tourniquet occlusion for 4 hr and all animals were sacrificed after 4 hr of reperfusion or at comparable times for the SHAMs. Soleus muscle cellular injury was determined by uptake of 99Tc pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of 125I-labeled albumin. Soleus muscle and lung neutrophil infiltration were measured with the myeloperoxidase assay. Serum samples were assessed for TNF-alpha production with the WEHI bioassay. Hindlimb I/R caused significant soleus muscle cellular injury, soleus muscle capillary injury, lung capillary injury, and lung neutrophil infiltration, Pretreatment with exogenous IL-10 significantly reduced soleus muscle capillary permeability and also reduced soleus muscle cellular injury, but not to a statistically significant degree. IL-10 administration also reduced pulmonary capillary permeability despite significantly increased lung neutrophil infiltration. Elevated TNF-alpha levels were found in 66% (4/6) rats in the I/R group versus 30% (3/10) rats in the I/R+IL-10 group. Exogenous IL-10 attenuates both local and distant organ injury after hindlimb I/R potentially independent of neutrophil infiltration.


Asunto(s)
Interleucina-10/farmacología , Daño por Reperfusión/fisiopatología , Animales , Permeabilidad Capilar , Miembro Posterior/irrigación sanguínea , Humanos , Pulmón/irrigación sanguínea , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , Masculino , Músculo Esquelético/irrigación sanguínea , Neutrófilos/patología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Factor de Necrosis Tumoral alfa/metabolismo
10.
Shock ; 6(3): 171-6, 1996 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8885081

RESUMEN

Acute visceral ischemia and subsequent reperfusion injury, which accompanies the surgical repair of a thoracoabdominal aorta aneurysm, is associated with high rates of morbidity and mortality. The purpose of the present study was to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) production contributes to organ dysfunction in animals subjected to visceral ischemia secondary to 30 min of supraceliac aortic occlusion. C57BL6/j mice were treated with either a TNF binding protein (TNF-bp-10 mg/kg) or an anti-IL-1 receptor type 1 antibody (150 micrograms) 2 h prior to 30 min of supraceliac aortic occlusion. An additional group of mice received 30 min of infrarenal aortic occlusion to determine the contribution of lower torso ischemia-reperfusion injury to the changes seen following supraceliac aortic occlusion. Visceral organ ischemia for 30 min produced by supraceliac aortic occlusion followed by 2 h of reperfusion produced measurable TNF-alpha in 38% of untreated mice, but TNF-alpha was undetectable in both sham-operated mice and following infrarenal aortic occlusion. After 2 h of reperfusion, lung myeloperoxidase levels were significantly elevated in the mice experiencing visceral ischemia-reperfusion compared with either a sham operation or infrarenal ischemia-reperfusion (11.6 +/- 1.3 U/g vs. 3.4 +/- .2 U/g and 3.7 +/- 1.0 U/g, respectively, p < .05). Pretreatment with TNF-bp and anti-IL-1 antibody decreased lung neutrophil recruitment (7.2 +/- 1.2 U/g and 4.6 +/- 1.1 U/g) and capillary membrane permeability changes in mice following visceral ischemia-reperfusion. The present study demonstrates that brief (30 min) clinically relevant visceral ischemia produces TNF-alpha and IL-1 dependent lung injury.


Asunto(s)
Interleucina-1/metabolismo , Lesión Pulmonar , Daño por Reperfusión/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Aorta Abdominal/cirugía , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Permeabilidad Capilar , Femenino , Interleucina-6/sangre , Interleucina-6/metabolismo , Hígado/lesiones , Hígado/metabolismo , Pulmón/irrigación sanguínea , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Peroxidasa/metabolismo , Factores de Tiempo , Procedimientos Quirúrgicos Vasculares/métodos
11.
Blood ; 88(3): 922-7, 1996 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-8704250

RESUMEN

Tumor necrosis factor-alpha (TNF-alpha) can bind to two distinct transmembrane receptors, the p55 and p75 TNF receptors. We compared the capability of two mutant TNF proteins with exclusive affinity for the p55 or p75 TNF receptor with that of wild type TNF, to activate the hemostatic mechanism in baboons. Both activation of the coagulation system, monitored by the plasma levels of thrombin-antithrombin III complexes, and activation of the fibrinolytic system (plasma levels of tissue-type plasminogen activator, and plasminogen activator inhibitor type I), were of similar magnitude after intravenous injection of wild type TNF or the TNF mutant with affinity only for the p55 receptor. Likewise, wild type TNF and the TNF p55 specific mutant were equally potent in inducing neutrophil degranulation (plasma levels of elastase-alpha 1-antitrypsin complexes). Wild type TNF tended to be a more potent inducer of secretory phospholipase A2 release than the p55 specific TNF mutant. Administration of the TNF mutant binding only to the p75 receptor did not induce any of these responses. We conclude that TNF-Induced stimulation of coagulation, fibrinolysis, neutrophil degranulation, and release of secretory phospholipase A2 are predominantly mediated by the p55 TNF receptor.


Asunto(s)
Antígenos CD/efectos de los fármacos , Coagulación Sanguínea/efectos de los fármacos , Fibrinólisis/efectos de los fármacos , Receptores del Factor de Necrosis Tumoral/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Animales , Antígenos CD/fisiología , Coagulación Sanguínea/fisiología , Fibrinólisis/fisiología , Elastasa de Leucocito , Mutagénesis Sitio-Dirigida , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Elastasa Pancreática/metabolismo , Papio/sangre , Fosfolipasas A/metabolismo , Fosfolipasas A2 , Mutación Puntual , Receptores del Factor de Necrosis Tumoral/fisiología , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis Tumoral , Proteínas Recombinantes/farmacología , Especificidad por Sustrato , Factor de Necrosis Tumoral alfa/genética
12.
J Exp Med ; 184(1): 165-71, 1996 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-8691130

RESUMEN

Tumor necrosis factor (TNF) is a potentially useful adjunct to anticancer therapies. However, the clinical utility of TNF has been limited by generalized toxicity and hypotension. Recently, studies have begun to dissect the individual proinflammatory and immunologic responses that result from TNF binding to its two cellular receptors, p55 and p75, in an attempt to develop TNF receptor agonists with reduced systemic toxicity. To evaluate a p75 receptor selective TNF mutant (p75TNF), TNF and p75TNF were administered to healthy anesthetized baboons. Intravenous infusion of the p75TNF produced none of the hemodynamic changes seen after the infusion of TNF. Infusion of p75TNF also failed to induce the plasma appearance of interleukins 6 and 8. However, p75TNF enhanced in vitro baboon thymocyte proliferation to concanavalin A, and infusion of p75TNF resulted in increased soluble p55 and p75 receptor plasma concentrations. Local skin necrosis and tissue neutrophil infiltration were seen after subcutaneous injections of TNF and p55TNF. Subcutaneous injection of p75TNF did not result in skin necrosis but did result in a modest dermal infiltration of lymphocytes and macrophages. The findings suggest that p75TNF may stimulate T cell proliferation without the systemic and local toxicity seen with TNF.


Asunto(s)
Antígenos CD/fisiología , Inflamación/etiología , Activación de Linfocitos , Receptores del Factor de Necrosis Tumoral/fisiología , Linfocitos T/inmunología , Animales , Antígenos CD/química , Unión Competitiva , Regulación de la Temperatura Corporal , Citocinas/metabolismo , Hemodinámica , Humanos , Papio , Receptores del Factor de Necrosis Tumoral/química , Receptores Tipo II del Factor de Necrosis Tumoral , Choque Séptico/etiología , Especificidad de la Especie , Factor de Necrosis Tumoral alfa/química
13.
Ann Surg ; 223(6): 729-34; discussion 734-6, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8645046

RESUMEN

OBJECTIVE: Repair of thoracoabdominal aortic aneurysms (TAAAs) is associated with significant postoperative morbidity and mortality. Reperfusion of acutely ischemic abdominal viscera in animals leads to release of multiple factors that cause local and distant organ damage, and similar phenomena occurring in humans after TAAA repair could contribute to the high morbidity/mortality and cost associated with this procedure. METHODS: Twenty-nine patients undergoing elective TAAA repair were studied prospectively. Preoperative organ dysfunction and intraoperative risk factors (cross-clamp time, blood loss, operative time) were assessed and compared with postoperative organ dysfunction (defined as: pulmonary, positive pressure ventilation for > 7 days; renal, increase in serum creatinine > 2.0 mg/dL over baseline; hepatic, lactate dehydrogenase > 500 international units and total bilirubin > 3.0 mg/dL or serum transaminase level > 200 international units; hematopoietic, platelet count > 50 K or leukocyte count > 4.5 K, mortality, and costs. RESULTS: No relationship between preoperative organ dysfunction, blood loss, or operative time and postoperative organ dysfunction or mortality was seen; however, cross-clamp times > 40 minutes were associated with a significantly greater incidence of pulmonary (59%), renal (47%), hepatic (35%), and hematopoietic (47%) dysfunction. In addition, multiple-organ dysfunction (> 2 organ systems) was more common after > 40 minutes of visceral ischemia and led to significantly greater overall hospital ($88,465 + $76,155 vs. $41,782 + $31,244) and intensive care unit ($26,726 + $28,256 vs. $11,234 + $12,146) costs (p < 0.01, Mann-Whitney U test). Mortality associated with leukopenia was 67% compared with 4% without leukopenia (p < 0.01). CONCLUSION: Increasing durations of acute visceral ischemia led to significant multiple organ dysfunction after TAAA repair. Methods of limiting visceral ischemia or the systemic effects of visceral ischemia may decrease both the morbidity and mortality and the overall hospital cost associated with this procedure.


Asunto(s)
Abdomen/irrigación sanguínea , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Isquemia/etiología , Insuficiencia Multiorgánica/etiología , Complicaciones Posoperatorias , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Femenino , Costos de Hospital , Humanos , Isquemia/economía , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/economía , Complicaciones Posoperatorias/economía , Estudios Prospectivos , Factores de Riesgo
14.
Blood ; 87(8): 3282-8, 1996 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-8605344

RESUMEN

Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.


Asunto(s)
Periodo Posoperatorio , Receptores de Interleucina-1/análisis , Sepsis/sangre , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/sangre , Aneurisma de la Aorta Torácica/cirugía , Colecistectomía Laparoscópica , Colelitiasis/sangre , Colelitiasis/cirugía , Colectomía , Enfermedad Crítica , Femenino , Humanos , Inflamación/sangre , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/cirugía , Proteína Antagonista del Receptor de Interleucina 1 , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/sangre , Receptores de Interleucina-1/clasificación , Sialoglicoproteínas/sangre , Solubilidad , Síndrome , Procedimientos Quirúrgicos Vasculares
15.
Reg Immunol ; 5(3-4): 158-64, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8240934

RESUMEN

Macrophages are a pivotal cell in the production of a variety of cytokines. In addition, macrophages express receptors on their surface which allows them to act as target cells for cytokines. The regulation of both cytokine production and cytokine receptor expression in macrophages may play a key role in modulating the processes of inflammation, injury, and repair. In this report we have studied the regulation of macrophage receptors for tumor necrosis factor-alpha (TNF alpha) on rat bone marrow-derived macrophages, rat alveolar macrophages, human monocyte-derived macrophages, and the human monocyte-like cell line, U937, by a variety of immunomodulatory and inflammatory agents. U937 cells and rat and human macrophages bound TNF alpha in a saturable process, with an affinity in each cell type of approximately 1 nM. Following incubation with phorbol myristate acetate for 60 min, TNF alpha binding to all cells was decreased. Interleukin-1 treatment increased TNF alpha binding to human and rat macrophages. Interferon-gamma treatment decreased receptor activity in both human and rat macrophages, but increased TNF alpha binding to U937 cells. Treatment of human and rat macrophages with endotoxin resulted in a rapid loss of TNF alpha binding, while endotoxin treatment increased receptor expression in U937 cells. In all cases, receptor regulation was the result of a change in receptor number. Finally, following intraperitoneal injection of endotoxin, TNF alpha receptor expression was down-regulated on alveolar lavage cells from rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Macrófagos/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Animales , Línea Celular Transformada , Células Cultivadas , Regulación hacia Abajo , Humanos , Lipopolisacáridos/toxicidad , Macrófagos/inmunología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Ratas , Toxemia/inducido químicamente , Toxemia/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
16.
Am J Respir Cell Mol Biol ; 7(4): 379-84, 1992 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1327012

RESUMEN

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) are secreted by macrophages in response to endotoxin challenge. In addition, macrophages express receptors for both of these cytokines. Macrophage function can therefore be modulated by regulation of both cytokine production and receptor levels. We have initiated studies to investigate the effects of TNF-alpha and IL-1 alpha on macrophage function. Macrophages were obtained by in vitro differentiation of rat bone marrow cells. The biologic response to TNF-alpha and IL-1 alpha was assessed by measurement of superoxide production quantitated by the reduction of cytochrome c in response to phorbol myristate acetate. Macrophages were treated with endotoxin (LPS), TNF-alpha, and IL-1 alpha, alone and in combination. None of these agents was a primary stimulus for superoxide production. However, after treatment with endotoxin or TNF-alpha for 24 h, macrophages were primed for enhanced production of superoxide. The priming effect of LPS was due, at least in part, to endogenously produced TNF-alpha, since anti-murine TNF-alpha antibodies blocked the LPS-mediated priming by approximately 30%. IL-1 alpha did not prime macrophages, but treatment with IL-1 alpha followed by TNF-alpha or LPS resulted in enhanced superoxide production. IL-1 alpha treatment of macrophages resulted in an increase in TNF-alpha receptors, which might explain the synergistic priming of TNF-alpha and IL-1 alpha.


Asunto(s)
Médula Ósea/metabolismo , Interleucina-1/farmacología , Macrófagos/metabolismo , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Animales , Anticuerpos , Células Cultivadas , Grupo Citocromo c/metabolismo , Sinergismo Farmacológico , Cinética , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratas , Proteínas Recombinantes/farmacología , Factor de Necrosis Tumoral alfa/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA