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1.
Arch Esp Urol ; 64(3): 219-26, 2011 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-21487172

RESUMEN

Approximately 4-14% pelvic fractures cause a posterior urethral injury. Pelvic fractures associated with straddle injuries or large trauma accidents are more frequently involved with this kind of lesions. Primary open repair of the urethral injury is discouraged in the acute setting. 3-6 months after urinary diversion a formal open reconstruction can be safely attempted. This gives time for scar maturation, reabsorption of pelvic hematomas, and relative restoration of anatomical fascial layers. The complexity of such interventions can be minimized following proper diagnostic and surgical protocols. Anastomotic urethroplasty under the precepts of the progressive perineal approach provides an excellent treatment option for these patients. The aim of this paper is the detailed description of the procedure for the treatment of such injuries.


Asunto(s)
Uretra/lesiones , Estrechez Uretral/cirugía , Anastomosis Quirúrgica/métodos , Fracturas Óseas/complicaciones , Humanos , Huesos Pélvicos/lesiones , Cuidados Posoperatorios , Resultado del Tratamiento , Estrechez Uretral/etiología
2.
Arch Esp Urol ; 64(3): 207-18, 2011 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-21487171

RESUMEN

Currently, we have different technical options for treating clinically complex scenarios such as neurogenic bladder, difficult to manage lower urinary tract obstruction and many disasters sometimes seen after prostate cancer treatment. During the seventies, clean intermittent bladder catheterization was established as the best treatment option for these patients. As a method, suprapubic urinary diversion has undergone a major evolution over the past fifty years trying to solve the most refractory and poor prognosis cases. Continent ileovesicostomy is an easy emptying and low-pressure non-catheterizable urinary conduit that enables safe and durable urine elimination. In this article a detailed and updated knowledge of this technique is provided.


Asunto(s)
Complicaciones Posoperatorias/cirugía , Derivación Urinaria/métodos , Enfermedades Urológicas/cirugía , Adulto , Cateterismo , Femenino , Humanos , Ileostomía , Laparoscopía , Masculino , Resultado del Tratamiento , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Vejiga Urinaria Neurogénica/cirugía , Retención Urinaria/etiología , Retención Urinaria/cirugía
3.
Thromb Haemost ; 83(3): 445-54, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10744152

RESUMEN

High circulating levels of the procoagulant molecule tissue factor (TF) are associated with thrombosis in a variety of diseases including unstable angina, cancer, and sepsis. Currently, there are no clinical assays to measure the level of TF activity in whole blood. We present an assay called Tissue Factor Clotting Time ("TiFaCT") that detects fibrin formation in human blood. The mean baseline clotting time in a healthy population was 472 +/- 94 s (mean +/- SD, n = 150). Bacterial lipopolysaccharide (LPS or endotoxin) shortened the clotting time in a time-dependent manner. Inhibitory anti-TF antibodies prolonged the clotting time of LPS-stimulated blood, indicating that the shortened clotting time was due to induction of TF expression. Patients with unstable angina had shortened mean baseline clotting time (284 +/- 86, n = 13) compared with healthy volunteers (474 +/- 98, n = 30), suggesting that these patients had elevated levels of circulating TF. The TiFaCT assay should prove clinically useful in quantifying the levels of circulating TF in patients at risk of thrombosis.


Asunto(s)
Análisis Químico de la Sangre/métodos , Tromboplastina/análisis , Adulto , Anciano , Angina Inestable/sangre , Angina Inestable/complicaciones , Animales , Anticuerpos/farmacología , Endotoxemia/sangre , Estudios de Evaluación como Asunto , Femenino , Humanos , Técnicas In Vitro , Lipopolisacáridos/toxicidad , Masculino , Persona de Mediana Edad , FN-kappa B/antagonistas & inhibidores , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Conejos , Proteínas Recombinantes/farmacología , Valores de Referencia , Factores de Riesgo , Tromboplastina/antagonistas & inhibidores , Tromboplastina/farmacología , Trombosis/sangre , Trombosis/etiología
4.
Int J Oncol ; 14(3): 501-8, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10024683

RESUMEN

Phenylbutyrate (PB) is a potent differentiating agent and currently under investigation for the treatment of prostate cancer (CaP) and other malignancies. We have studied the impact of PB in vitro and in vivo on differentiation, proliferation and apoptosis in the LNCaP and LuCaP 23.1 prostate cancer xenograft models. In vitro we found that i) PB increased PSA secretion/cell, ii) inhibited cell proliferation in a time- and dose-dependent manner resulting in a cell cycle arrest in G1-phase and iii) induced apoptosis at concentrations of 2.5 mM after 3 days of treatment. In PB treated animals tumor growth stabilized or regressed. Combination of castration and PB treatment had a synergistic antiproliferative effect. The growth-inhibitory and differentiating properties and a low toxicity profile of PB provide rationale for further clinical studies in patients with CaP.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Fenilbutiratos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Andrógenos/farmacología , Animales , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Trasplante Heterólogo , Células Tumorales Cultivadas
5.
Urology ; 49(4): 536-40, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9111622

RESUMEN

OBJECTIVES: To determine if well-differentiated colonic-type adenocarcinoma of the urachus behaves in a benign fashion, and thus might be treated by segmental rather than radical cystectomy. METHODS: A retrospective review of the literature since 1863 with one added case review is presented here. Only cases with photomicrograph confirmation were accepted. RESULTS: Sixteen previously reported patients with well differentiated colonic-type adenocarcinoma of the urachus were treated by partial cystectomy. None were treated by radical cystectomy. Most (88%) of these patients were cured, whereas all patients (100%) treated in the last 45 years were cured. CONCLUSIONS: These data support a more limited approach to the surgical excision of these benign-appearing tumors. The influence of this histologic type on the prognosis of patients with urachal tumors has not been previously reported.


Asunto(s)
Adenocarcinoma Mucinoso/cirugía , Cistectomía , Uraco/cirugía , Anciano , Cistectomía/métodos , Femenino , Humanos , Estudios Retrospectivos
8.
Unfallchirurg ; 108(10): 821-8, 2005 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-16151747

RESUMEN

BACKGROUND: Within the S3 Guideline Project of the European Association of Urology (EAU) an expert committee was set up to develop guidelines for the appropriate management of genitourinary trauma. These European guidelines were accepted in principle as national guidelines by the German Urological Society. Therefore, they also became the basis of the contribution of the German Urological Society to the S3 Guideline Project "Polytrauma" of the German Society for Trauma Surgery. METHOD: For the guideline "management of genitourinary trauma" all the requirements for classification as S3 guidelines were full-filled. The guideline itself was developed in accordance with the principles of "evidence-based medicine". A systematic analysis of literature published between 1966 and 2004 was carried out. The articles retrieved were assessed in respect of study design and clinical relevance and classified following the scheme of the Centre for Evidence-Based Medicine in Oxford. CONCLUSION: In suspected renal injuries the hemodynamic situation of the patient is the benchmark for the diagnostic and therapeutic algorithm. The diagnostic gold standard for the assessment of haemodynamically stable patients is CT scanning. Uncontrolled haemodynamic instability is an indication for immediate explorative laparotomy. Partial ureteral tears are managed by stenting; complete tears by immediate surgical repair. Pelvic fractures are often associated with bladder ruptures. Extraperitoneal bladder ruptures, identified by retrograde cystography, are in most cases safely managed by simple catheter drainage. Intraperitoneal ruptures require surgical intervention. Blood at the meatus may suggest a urethral lesion-blind urethral catheterization should not be attempted. Suprapubic cystostomy and delayed urethroplasty are recommended.


Asunto(s)
Traumatismo Múltiple/diagnóstico , Traumatismo Múltiple/terapia , Pautas de la Práctica en Medicina/normas , Sistema Urinario/lesiones , Sistema Urinario/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Procedimientos Quirúrgicos Urológicos/normas , Alemania , Humanos , Guías de Práctica Clínica como Asunto , Urografía/normas
9.
World J Surg ; 25(12): 1565-72, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11775193

RESUMEN

Of our last 2483 renal trauma patients, 113 had grade IV injuries. In most the mechanism was a penetrating injury (60%: 30% gunshot, 30% stab wounds). Associated injuries were common (80%) and hospital stays prolonged, averaging 16 days. Most of the patients (70%) required transfusion, some massively (average volume 4.4 liters, range 0-30 liters). Surprisingly, not all patients with grade IV renal injuries had gross hematuria: 25% had microhematuria, and 4% had neither microscopic nor gross hematuria. Computed tomography (CT) diagnosed the injury correctly in 100% of the patients in whom it was performed; when CT was not available, "one-shot" intraoperative intravenous pyelography (IVP) demonstrated grossly abnormal findings in 90%. Renal exploration was performed in 78%, resulting in 69% renorrhaphy and 9% nephrectomy rates in our 113 patients. Almost all those with penetrating trauma required exploration (97%), whereas only 50% of those with blunt trauma did so. The overall complication rate and kidney-specific complication rate did not differ significantly between patients who were observed and those who underwent surgery. Complications rates were similar in grade IV renal laceration patients and grade III patients. Delayed complications after hospital discharge were not seen, although follow-up was rare in this inner-city trauma population. Among the 21% of patients in whom postoperative nucleotide renal function scans were available, function was generally good (average 36%). Only patients who underwent concomitant vascular repair had poor function (below 20%).


Asunto(s)
Riñón/lesiones , Laceraciones/cirugía , Heridas Penetrantes/cirugía , Traumatismos Abdominales/clasificación , Traumatismos Abdominales/diagnóstico por imagen , Traumatismos Abdominales/cirugía , Humanos , Puntaje de Gravedad del Traumatismo , Riñón/diagnóstico por imagen , Riñón/fisiopatología , Pruebas de Función Renal , Laceraciones/diagnóstico por imagen , Tiempo de Internación , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/cirugía , Heridas Penetrantes/fisiopatología
10.
J Urol ; 163(4): 1076-84, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10737470

RESUMEN

PURPOSE: We review the literature on gentamicin, including single daily dosing and "switch" therapy. MATERIALS AND METHODS: We used MEDLINE to search the literature from 1966 to June 1997, and then manually searched bibliographies to identify studies that our initial search might have missed. RESULTS: Gentamicin has attractive characteristics, including wide spectrum, infrequent resistance, economy and familiarity. Although limited by well known toxicities, gentamicin remains a drug of choice for serious Gram-negative infections. Dosing strategies, such as single daily dosing and switch therapy, have renewed enthusiasm for this time-honored drug. CONCLUSIONS: Gentamicin remains a valuable drug in urology. Once daily dosing and switch therapy offer the potential to increase effectiveness and convenience while decreasing toxicity and costs.


Asunto(s)
Aminoglicósidos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Gentamicinas/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Aminoglicósidos/farmacología , Gentamicinas/farmacología , Humanos
11.
J Urol ; 153(3 Pt 1): 745-7, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7861528

RESUMEN

To our knowledge pyocele of the scrotum after spontaneous bacterial peritonitis has not been reported previously. We describe this unusual condition, and discuss diagnosis, pathophysiology and treatment.


Asunto(s)
Infecciones por Escherichia coli , Peritonitis/microbiología , Escroto , Enfermedades de los Genitales Masculinos/microbiología , Humanos , Masculino , Persona de Mediana Edad , Peritonitis/complicaciones , Supuración/microbiología
12.
Urology ; 56(2): 331, 2000 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-10925113

RESUMEN

Penile augmentation by injection of petroleum jelly is still performed by nonmedical practitioners abroad and causes foreign body reactions with resultant scarring, deformity, and ulceration. Surgical treatment involves removal of the foreign material and granuloma, followed by scrotal flaps, inguinal flaps, free flaps, or split-thickness skin grafts. We present the use of native penile skin for coverage after resection of oleogranuloma in the first case of which we are aware. Local penile skin coverage allows for an excellent surgical result, with many potential advantages over flaps or skin grafts.


Asunto(s)
Procedimientos Quirúrgicos Dermatologicos , Granuloma de Cuerpo Extraño/etiología , Granuloma de Cuerpo Extraño/cirugía , Enfermedades del Pene/etiología , Pene/cirugía , Vaselina/efectos adversos , Adulto , Emigración e Inmigración , Humanos , Masculino , Enfermedades del Pene/cirugía , Pene/efectos de los fármacos , Vaselina/administración & dosificación , Cirugía Plástica
13.
Urology ; 54(2): 252-7, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10443720

RESUMEN

OBJECTIVES: To compare the urodynamic parameters and continence rates among five different continent urinary reservoirs. METHODS: Continent urinary reservoirs were constructed in 40 patients with an average age of 60 years (range 23 to 81). Twenty-three had orthotopic neobladders ("neobladders"), and in 17 the reservoirs exited by way of an abdominal wall stoma as "stomal urinary reservoirs." In the neobladders, the detubularized segment was ileum (Hautmann) in 5, ileocecal (Mainz) in 8, sigmoid in 4, and gastric in 6. In the stomal urinary reservoirs, the segment was ileocecal in 11 (Mainz) and right colon in 6 (Indiana). Urodynamic studies were performed at a mean of 9.1 months. RESULTS: Stomal urinary reservoirs had the best continence rates (Indiana pouch 100%, Mainz pouch 91%). Neobladder continence rates were as follows: Hautmann, 80%; Mainz, 75%; sigmoid, 50%; and gastric, 33%. Day and night incontinence rates were nearly identical. Compared with the other pouches, gastric and sigmoid reconstructions had the smallest capacity, were the least compliant, and were the most contractile. CONCLUSIONS: Stomal urinary reservoirs using ileocecal valve and right colon, with or without an overlying patch of ileum, provide similar excellent results. Continence approached 100% in compliant patients without the need for revision. Patients with neobladders were less continent, although those with ileal or ileocecal configurations still had very good continence rates. Neobladders of sigmoid or stomach can be used when necessary, but with greater incontinence rates. This poorer continence can be explained by the decreased capacity, decreased compliance, and a tendency toward high pressure spikes despite detubularization.


Asunto(s)
Reservorios Urinarios Continentes/fisiología , Urodinámica , Adulto , Anciano , Anciano de 80 o más Años , Colon/trasplante , Colon Sigmoide/trasplante , Humanos , Íleon/trasplante , Masculino , Persona de Mediana Edad , Estómago/trasplante
14.
J Trauma ; 50(2): 195-200, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11242281

RESUMEN

BACKGROUND: We queried an observational database of renal trauma patients to validate the organ injury severity scale (kidney) of the American Association for the Surgery of Trauma (AAST). METHODS: In a retrospective review of our renal trauma database (2,467 patients) with 58 clinical and radiographic patient variables, statistical "classification trees" were used to determine factors predicting need for surgical repair. RESULTS: Scales correlated with the need for surgery (grade I = 0%, grade II = 15%, grade III = 76%, grade IV = 78%, and grade V = 93%) and for nephrectomy (grade I = 0%, grade II = 0%, grade III = 3%, grade IV = 9%, and grade V = 86%). Classification tree analysis (confirmed in 83 additional patients) identified the AAST organ injury severity scale as the most important variable predicting the need for renal repair. CONCLUSION: In a retrospective review of more than 2,500 patients, we determined that the AAST organ injury severity scale correlates with the need for kidney repair or removal. Classification tree analysis confirmed the scale as the prime variable predicting need for surgical repair.


Asunto(s)
Puntaje de Gravedad del Traumatismo , Riñón/lesiones , Algoritmos , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Modelos Logísticos , Masculino , Estudios Retrospectivos
15.
J Urol ; 164(2): 356-9, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10893584

RESUMEN

PURPOSE: Orthotopic neobladders are most commonly formed from colon and/or small bowel segments. However, after excellent results were reported in children, we constructed gastric neobladders in select men who had undergone cystectomy. Although gastric neobladders in adults have been reported to have decreased capacity, to our knowledge neither long-term followup nor urodynamic parameters have been reported in these patients. MATERIALS AND METHODS: Gastric neobladder was performed in 8 patients following cystectomy for malignancy in 7 and undiversion in 1. Average followup was 43 months and all patients underwent urodynamic evaluations an average of 9.1 months after surgery. Patients also completed an incontinence questionnaire. The gastric neobladder group was compared to a similar group of patients who underwent neobladder construction from either small bowel (Kock/Hautmann/Studer) or ileocecal segments (Mainz). RESULTS: The gastric neobladder group had significantly reduced mean bladder capacity compared to the ileal or ileocecal neobladder group (309 versus 551 cc, respectively, t = 0.001), while compliance was similarly decreased (27 versus 59 cc/cm. H2O, respectively, t = 0.04). Incontinence rates were greater in the gastric neobladder group (63%) compared to the ileal or ileocecal neobladder group (8% to 23%, t = 0.02). Complication rates were comparable. Revision or removal was required in 3 (38%) patients for severe incontinence, intractable dysuria and ureterogastric anastomotic stricture, respectively. CONCLUSIONS: Adult gastric neobladders as currently constructed are associated with poor urodynamic parameters and high incontinence rates. Routine use of gastric neobladders in adults is not recommended. They may be appropriate, especially as composites, in select cases such as renal failure or inadequate bowel length. The reasons for success in some patients and not in others are unknown.


Asunto(s)
Estómago/cirugía , Reservorios Urinarios Continentes , Urodinámica , Adulto , Anciano , Cistectomía , Estudios de Seguimiento , Humanos , Masculino , Métodos , Persona de Mediana Edad , Reoperación , Neoplasias de la Vejiga Urinaria/cirugía , Incontinencia Urinaria
16.
J Urol ; 151(5): 1301-7, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8158775

RESUMEN

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p < 0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.


Asunto(s)
ADN de Neoplasias/genética , Ploidias , Neoplasias de la Próstata/patología , Núcleo Celular/ultraestructura , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Pronóstico , Neoplasias de la Próstata/genética
17.
BJU Int ; 93(7): 937-54, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15142141

RESUMEN

OBJECTIVE: To determine the optimal evaluation and management of renal injuries by review of the world's English-language literature on the subject. METHODS: A consensus conference convened by the World Health Organization and the Societé Internationale d'Urologie met to critically review reports of the diagnosis and treatment of renal trauma. The English-language literature about renal trauma was identified using Medline, and additional cited works not detected in the initial search obtained. Evidence-based recommendations for the diagnosis and management of renal trauma were made with reference to a five-point scale. RESULTS: There were many Level 3 and 4 citations, few Level 2, and one Level 1 which supported clinical practice patterns. Findings of nearly 200 reviewed citations are summarized. CONCLUSIONS: Published reports on renal trauma still rely heavily on expert opinion and single-institution retrospective case series. Prospective trials of the most significant issues, when possible, might improve the quality of evidence that dictates the behaviour of practitioners.


Asunto(s)
Riñón/lesiones , Heridas no Penetrantes/cirugía , Heridas Penetrantes/cirugía , Diagnóstico por Imagen/métodos , Embolización Terapéutica/métodos , Humanos , Puntaje de Gravedad del Traumatismo , Heridas no Penetrantes/complicaciones , Heridas Penetrantes/complicaciones
18.
Prostate ; 43(1): 63-70, 2000 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-10725867

RESUMEN

BACKGROUND: Intermittent androgen suppression (IAS) has been proposed as a method of delaying the onset of androgen-independent growth in prostate cancer. While several pilot studies have demonstrated the feasibility of such a treatment, no study to date has defined the effect of IAS on survival. METHODS: We developed an IAS protocol for mice bearing the LuCaP 23.12 human prostate cancer xenograft, with each cycle consisting of 1 week of androgen replacement with a testosterone pellet followed by 3 weeks of androgen withdrawal. Mice that responded to castration with a 40% or greater decrease in serum prostate-specific antigen (PSA) were randomized to treatment with either continuous androgen suppression (CAS) or IAS. Serum PSA, tumor volume, and overall survival were monitored. RESULTS: A total of 75 mice met the randomization criteria. There was no significant difference of survival between animals treated with CAS or IAS (185 vs. 239 days, P = 0.1835). Serum PSA showed evidence of cycling with hormonal manipulation. No cycling was noted in tumor volume. CONCLUSIONS: IAS is not associated with a decrease in survival compared to CAS, yet in patients may offer quality-of-life improvements. Further studies of IAS in the setting of Institutional Review Board (IRB) approved clinical trials should be encouraged. Prostate 43:63-70, 2000. Published 2000 Wiley-Liss, Inc.


Asunto(s)
Neoplasias de la Próstata/tratamiento farmacológico , Testosterona/administración & dosificación , Animales , Esquema de Medicación , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Distribución Aleatoria , Testosterona/uso terapéutico , Trasplante Heterólogo
19.
Am J Pathol ; 157(6): 1849-62, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11106558

RESUMEN

Functional inhibition of tissue factor (TF) has been shown to improve coronary blood flow after myocardial ischemia/reperfusion (I/R) injury. TF initiates the coagulation protease cascade, resulting in the generation of the serine protease thrombin and fibrin deposition. Thrombin can also contribute to an inflammatory response by activating various cell types, including vascular endothelial cells. We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I/R injury. At-risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes, which was associated with a low level of extravascular fibrin deposition. Functional inhibition of TF activity with an anti-rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61% (P = 0.004) and 44% (P = 0.014), respectively. Similarly, we found that inhibition of thrombin with hirudin reduced infarct size by 59% (P = 0.014). In contrast, defibrinogenating the rabbits with ancrod had no effect on infarct size, suggesting that fibrin deposition does not significantly contribute to infarct size. Functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration. We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R.


Asunto(s)
Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Isquemia Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/complicaciones , Miocarditis/etiología , Trombina/fisiología , Tromboplastina/fisiología , Animales , Anticuerpos Monoclonales/farmacología , Antitrombinas/farmacología , Movimiento Celular/fisiología , Quimiocinas/antagonistas & inhibidores , Fibrina/metabolismo , Fibrinógeno/metabolismo , Hirudinas/farmacología , Microscopía Electrónica , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocarditis/prevención & control , Miocardio/patología , Neutrófilos/fisiología , Conejos , Trombina/antagonistas & inhibidores , Tromboplastina/antagonistas & inhibidores , Tromboplastina/inmunología
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