RESUMO
Despite intensive investigation, the pathogenesis of post-injury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly suggests that the gastrointestinal tract (i.e., the gut) plays a pivotal pathogenic role. Since its inception in 1988, the Trauma Research Center (TRC) at the University of Texas-Houston Medical School (UTHMS) has focused its efforts on elucidating the role of the gut in post-injury MOF. On the basis of our observations and those of others, we believe that 1) shock with resulting gut hypoperfusion is an important inciting event, 2) the reperfused gut is a source of proinflammatory mediators that can amplify the early systemic inflammatory response syndrome (SIRS) and thus contribute to early MOF, 3) early gut hypoperfusion causes an ileus in both the stomach and small bowel that sets the stage for progressive gut dysfunction so that the proximal gut becomes a reservoir for pathogens and toxins that contribute to late sepsis-associated MOF, and 4) late infections cause further worsening of this gut dysfunction. Thus, the gut can be both an instigator and a victim of MOF. The purpose of this article is to provide the rationale behind these beliefs and to provide a brief overview of the ongoing research projects in the TRC at UTHMS.
Assuntos
Sistema Digestório/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Ferimentos e Lesões/complicações , Animais , Sistema Digestório/lesões , Mucosa Gástrica/fisiopatologia , Gastroenterite/imunologia , Gastroenterite/metabolismo , Gastroenterite/fisiopatologia , Humanos , Perfusão , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologiaRESUMO
The efficacy of infrainguinal bypass for limb salvage in young diabetic patients has not been well established. The purpose of this study is to determine the intermediate-term results (patency and limb salvage) of infrainguinal revascularization carried out for limb salvage (rest pain or ulceration) in young (<50 years old) diabetic atherosclerotic patients. Thirty-nine bypasses in 31 patients with a mean age of 44 years were retrospectively reviewed. There were no perioperative deaths. Minor or major complications occurred in 23% of cases. By life table analysis, the 18-month primary patency rate was 60+/-11%, assisted primary patency rate was 78+/-9%, and limb salvage rate was 71+/-9%. Most major amputations (five of nine) were required in patients with functional bypasses, either because of persistent infection or failure of wound healing. The presence of severe stenoses (>70%) in all three major named foot vessels (dorsalis pedis, medial and lateral plantar arteries) was associated with a high likelihood of limb loss despite a patent bypass (p<0.05). We could not identify any other factors statistically predictive of thrombosis, amputation, or the need for graft revision. Infrainguinal revascularization in this patient population can be carried out with acceptable limb salvage rates. However, patients should be made aware of the high incidence of amputation regardless of the success of the revascularization procedure, particularly in the presence of severe occlusive disease within the foot.
Assuntos
Arteriosclerose/cirurgia , Angiopatias Diabéticas/cirurgia , Doenças Vasculares Periféricas/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Feminino , Artéria Femoral/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Artérias da Tíbia/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
Inducible nitric oxide synthase (NOS 2) is thought to play a role in gut motility disorders that occur under proinflammatory conditions. Clinically, ileus occurs after sepsis and shock-induced gut ischemia/reperfusion (I/R). The purpose of this study was to determine if NOS 2 mediates impaired intestinal transit in well-established models of both moderate and severe gut ischemia/reperfusion. At laparotomy, Sprague-Dawley rats had duodenal catheters placed. Small intestinal transit was determined by quantitating the percentage tracer (FITC-dextran) in 10 equal segments of intestine 30 min after catheter injection [expressed as the mean geometric center (MGC) of distribution]. Transit was assessed at 6 and 24 h after gut ischemia [45 or 75 min of superior mesenteric artery occlusion (SMAO) with sham laparotomy as control]. In a separate set of experiments, N(6)-(iminoethyl)-L-lysine (L-NIL), a selective NOS 2 antagonist, was administered 1 h prior to laparotomy and transit was determined after 6 h as described above. Ileal NOS 2 expression was assessed by Western immunoblot and quantitative "real-time" RT-PCR. We observed that both 45 and 75 min of SMAO decreased intestinal transit at 6 h of reperfusion compared to sham. Ileal NOS 2 mRNA and protein were increased after 75, but not 45, min of SMAO. In addition, L-NIL improved transit after 75, but not 45, min of SMAO. We conclude that (1) NOS 2 is upregulated in the gut only after more severe ischemic insults, and (2) ileus is mediated, at least in part, by NOS 2 under these conditions.
Assuntos
Obstrução Intestinal/metabolismo , Intestino Delgado/enzimologia , Óxido Nítrico Sintase/genética , Traumatismo por Reperfusão/metabolismo , Animais , Anticorpos , Inibidores Enzimáticos/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Regulação Enzimológica da Expressão Gênica , Obstrução Intestinal/tratamento farmacológico , Intestino Delgado/irrigação sanguínea , Lisina/análogos & derivados , Lisina/farmacologia , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/imunologia , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/análise , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: chronic aortic dissection has long been considered a risk factor for neurologic deficit following thoracoabdominal aortic aneurysm (TAA) surgery. We reviewed our experience with regard to aneurysm extent and the use of adjunct, (distal aortic perfusion/cerebrospinal fluid drainage), and examined the impact of these factors on neurologic deficit among chronic dissection and non-dissection cases. METHODS: between February 1991 and March 2001, we repaired 800 aneurysms of the descending thoracic and thoracoabdominal aorta. Seven hundred and twenty-nine cases were elective; 196 chronic dissection, 533 non-dissection. 182/729 (24.9%) were TAA extent II. Among these, 61/182 (33%) involved chronic dissection. Adjunct was used in 507/729 (69.6%). We conducted detailed multivariate analyses to isolate the impact of chronic aortic dissection on neurologic morbidity, with other important risk factors taken into account. RESULTS: overall, 32/729 (4.4%) patients had neurologic deficit upon awakening; 7/196 (3.6%) in chronic dissections, and 25/533 (4.7%) in non-dissections. Adjunct had a major effect, reducing neurologic deficit in TAA extent II from 10/36 (27.8%) to 10/146 (6.9%) (p=0.001). However, in univariate and multivariate analysis, chronic dissection did not increase the risk of neurologic deficit, regardless of extent or mode of treatment. CONCLUSION: in contrast to previous reports, we determined that chronic aortic dissection is not a risk factor in TAA patients.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Doenças da Aorta/complicações , Dissecação/efeitos adversos , Doenças do Sistema Nervoso/etiologia , Doença Crônica , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: We have shown that both intraischemic hypothermia and hypertonic saline resuscitation provide dramatic protection against gut ischemia/reperfusion (I/R) injury that is in part mediated by heme oxygenase-1 (HO-1). We therefore hypothesized that induction of HO-1 by hemin would lessen damage and improve function after gut I/R. MATERIALS AND METHODS: Male Sprague-Dawley rats were treated with 50 micromol/kg hemin (HO-1 inducer ferric protoporphyrin IX chloride) sq or vehicle 2 h before superior mesenteric artery occlusion for 60 min or sham laparotomy. After 6 h of reperfusion, transit was determined by quantitation of percentage of tracer in 10 equal segments of small intestine 30 min following injection into the duodenum (expressed as mean geometric center). Ileum was harvested for assessment of mucosal histologic injury (Chiu score 0-5 by blinded observer), myeloperoxidase activity (MPO, index of inflammation), and HO-1 protein expression. RESULTS: Hemin treatment was associated with increased HO-1 protein expression, lessened mucosal injury, decreased MPO activity, and improved intestinal transit following gut I/R. CONCLUSION: These data corroborate that HO-1 plays an important role in protecting the gut against I/R-induced injury.