RESUMO
The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.2-3. Their strong homology and close physical location indicate a recent duplication of the original gene. Messenger RNA and protein expression patterns demonstrate that the DC-SIGN-related molecule is highly expressed on liver sinusoidal cells and in the lymph node but not on DCs, in contrast to DC-SIGN. Therefore, we suggest that a more appropriate name for the DC-SIGN-related molecule is L-SIGN, liver/lymph node-specific ICAM-3-grabbing nonintegrin. We show that in the liver, L-SIGN is expressed by sinusoidal endothelial cells. Functional studies indicate that L-SIGN behaves similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in trans. We propose that L-SIGN may play an important role in the interaction between liver sinusoidal endothelium and trafficking lymphocytes, as well as function in the pathogenesis of HIV-1.
Assuntos
Antígenos CD , Antígenos de Diferenciação , Moléculas de Adesão Celular/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , HIV-1/fisiologia , Lectinas Tipo C , Lectinas/fisiologia , Fígado/metabolismo , Receptores de Antígenos/fisiologia , Receptores de HIV/fisiologia , Receptores Virais/fisiologia , Animais , Sequência de Bases , Linhagem Celular , Células Cultivadas , Mapeamento Cromossômico , DNA Complementar , Células Dendríticas , Endotélio/citologia , Éxons , HIV-1/metabolismo , Humanos , Lectinas/genética , Lectinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Polimorfismo Genético , Receptores de Antígenos/genética , Receptores de Antígenos/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores de HIV/genética , Receptores de HIV/metabolismoRESUMO
Several studies suggest that normothermic ("warm") bypass techniques may improve myocardial outcomes for patients undergoing cardiac operations. Normothermic temperatures during cardiopulmonary bypass may, however, decrease the brain's tolerance to the ischemic insults that accompany all cardiac procedures. To assess the effect of bypass temperature management strategy on central nervous system outcomes in patients undergoing coronary revascularization, 138 patients were randomly assigned to two treatment groups: (1) hypothermia (n = 70), patients cooled to a temperature less than 28 degrees C during cardiopulmonary bypass, or (2) normothermia (n = 68), patients actively warmed to a temperature of at least 35 degrees C. Patients underwent detailed neurologic examination before the operation, on postoperative days 1 to 3 and 7 to 10, and at approximately 1 month after operation. In addition, a battery of five neuropsychologic tests was administered before operation, on postoperative days 7 to 10, and at the 4- to 6-week follow-up visit. Patients in the normothermic treatment group were older (65 +/- 10 vs 61 +/- 11 years in the hypothermic group), had statistically less likelihood of preexisting cerebrovascular disease, and had higher bypass blood glucose values (276 +/- 100 mg/% vs. 152 +/- 66 mg/% in the hypothermic group). All other patient characteristics and intraoperative variables were similar in the two treatment groups. Seven of 68 patients in the normothermic group were found to have a central neurologic deficit, compared with none of the patients cooled to 28 degrees C (p = 0.006). Performance on at least one neuropsychologic test deteriorated in the immediate postoperative period in more than one half of all patients in both treatment groups but returned to preoperative levels approximately 1 month after the operation in most (85%). This pattern was not related to bypass temperature management strategy. We conclude that active warming during cardiopulmonary bypass to maintain systemic temperatures > or = 35 degrees C increases the risk of perioperative neurologic deficit in patients undergoing elective coronary revascularization.
Assuntos
Temperatura Corporal , Encéfalo/fisiopatologia , Ponte Cardiopulmonar , Revascularização Miocárdica , Coluna Vertebral/fisiopatologia , Fatores Etários , Idoso , Glicemia/análise , Isquemia Encefálica/prevenção & controle , Transtornos Cerebrovasculares/complicações , Cognição/fisiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Seguimentos , Humanos , Hipotermia Induzida , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Exame Neurológico , Neuropsicologia , Resultado do TratamentoRESUMO
During a 12-year period, 313 patients with duodenal injuries were treated. Primary repair, pyloric exclusion, and gastrojejunostomy were used in 128 patients (41%) with severe duodenal and pancreaticoduodenal injuries, to reduce "duodenal" morbidity and mortality. The duodenal fistula rate was 2.2% overall, and 5.5% in the patients undergoing exclusion. Only two deaths were due to fistulas. Forty-two patients underwent upper gastrointestinal tract examinations after operation. In patients examined 21 days or more after operation, 94% had a patent pylorus. Marginal ulceration was infrequent (four patients), as were complications associated with the procedure (3%). Pyloric exclusion with gastrojejunostomy is a quick and simple procedure that allows return of pyloric patency and is associated with a low incidence of duodenal fistulas. When fistulas do develop, they are usually easily controlled and are associated with a low mortality. We believe pyloric exclusion with gastrojejunostomy to be the procedure of choice in patients with severe duodenal and pancreaticoduodenal trauma.
Assuntos
Duodeno/cirurgia , Jejuno/cirurgia , Piloro/cirurgia , Ferimentos e Lesões/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Duodeno/lesões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/mortalidadeRESUMO
Amino acid flux across the lungs was studied in humans to gain further insight into the altered nitrogen metabolism that characterizes catabolic disease states. Lung flux of glutamine, glutamate, and alanine was determined in three groups of surgical patients with indwelling pulmonary artery catheters: (1) preoperative controls (n = 14), (2) postoperative elective general surgical patients (n = 10, and (3) hyperdynamic septic surgical patients (n = 17). In controls the lung was an organ of amino acid balance. These exchange rates did not change in general surgical patients. In the septic group, glutamine release by the lung increased markedly from a control value of 0.80 +/- 0.99 mumol/kg per minute to 6.80 +/- 1.32 mumol/kg per minute. This accelerated release rate was secondary to both an increase in total pulmonary blood flow and an increase in the pulmonary artery-systemic arterial concentration difference. The lung also became an organ of significant alanine release in septic patients. The lung plays an active metabolic role in the processing of amino acids and may be a key regulator in interorgan nitrogen flux after major injury and infection.
Assuntos
Alanina/farmacocinética , Infecções Bacterianas/metabolismo , Glutamina/farmacocinética , Pulmão/metabolismo , Alanina/sangue , Amônia/sangue , Débito Cardíaco , Cateterismo de Swan-Ganz , Glutamatos/sangue , Ácido Glutâmico , Glutamina/sangue , Humanos , Período Pós-Operatório , Procedimentos Cirúrgicos OperatóriosRESUMO
The case of a 69-year-old man with aneurysms of the ascending aorta, transverse aortic arch, and thoracoabdominal aorta combined with coronary artery disease, aortic insufficiency, and severe aortoiliac occlusive disease is presented. Femoral arterial cannulation was contraindicated owing to the aortoiliac disease. Successful surgical treatment is described using an alternate method of cannulation and perfusion.
Assuntos
Aneurisma Aórtico/cirurgia , Arteriopatias Oclusivas/cirurgia , Doença das Coronárias/cirurgia , Artéria Ilíaca , Idoso , Aorta Abdominal , Aorta Torácica , Aneurisma Aórtico/complicações , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/cirurgia , Arteriopatias Oclusivas/complicações , Prótese Vascular , Ponte Cardiopulmonar , Cateterismo/métodos , Doença das Coronárias/complicações , Humanos , MasculinoRESUMO
BACKGROUND: Aneurysms of the ascending, arch, and descending thoracic aorta are typically managed with two operations. The first stage involves replacement of the ascending and arch aorta leaving a segment of graft in the proximal descending aorta with a mortality and stroke risk of 8%. The second stage involves replacement of the descending aorta with a mortality of 5% and a paraplegia risk of 5% to 10%. Some patients refuse surgical completion and others are at increased risk to undergo the second stage thoracotomy, leaving them with untreated descending thoracic aortic aneurysms vulnerable to rupture. A single-stage transmediastinal operation used in 14 patients is described. METHODS: Under circulatory arrest, the descending thoracic aorta is opened. A wire is passed up to the arch and a graft is brought down and secured excluding the descending thoracic aneurysm. The arch vessels are attached as a single patch and the graft is brought forward, replacing the ascending aorta. RESULTS: Fourteen patients have undergone single-stage replacement of the ascending, arch, and descending aorta with a 14% mortality rate and 14% incidence of paraplegia. CONCLUSIONS: Patients with aneurysms of the ascending, arch, and descending thoracic aorta can be managed with a single operation with comparable mortality and morbidity of the two-stage approach.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Reoperação , Taxa de Sobrevida , Técnicas de Sutura , Tomografia Computadorizada por Raios XRESUMO
From March 1991 through July 1992, 1,001 patients having elective coronary artery bypass grafting were randomized to receive either continuous warm (> or = 35 degrees C) blood cardioplegia with systemic normothermia (> or = 35 degrees C) or intermittent cold (< or = 8 degrees C) oxygenated crystalloid cardioplegia and moderate systemic hypothermia (< or = 28 degrees C). Preoperative variables including age, sex, prior coronary bypass grafting, hypertension, prior myocardial infarction, diabetes, angina class, and preoperative heart failure class were similar in both groups, as were the intraoperative variables of number of coronary grafts, mammary artery use, and cardiopulmonary bypass time. Aortic cross-clamp time was significantly longer in the warm group (46 +/- 23 minutes versus 40 +/- 21 minutes). Most postoperative variables including mortality (warm, 1.0%, and cold, 1.6%), Q wave infarction (warm, 1.4%, and cold, 0.8%), and need of an intraaortic balloon pump (warm, 1.4%, and cold, 2.0%) were similar between groups. Total neurologic events (warm, 4.5%, and cold, 1.4%; p < 0.005) and perioperative strokes (warm, 3.1%, and cold, 1.0%; p < or = 0.02) were significantly higher in the warm group. Neurologic events included perioperative stroke (warm, 15 patients, and cold, 5 patients; p < 0.02), perioperative encephalopathy (warm, 2 patients, and cold, 1 patient), and delayed (> or = 3 in-hospital days) stroke (warm, 5 patients, and cold, 1 patient). All patients experiencing a stroke had a persistent neurologic deficit at the time of discharge. Encephalopathy resolved completely in all instances.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Sangue , Doenças do Sistema Nervoso Central/etiologia , Ponte de Artéria Coronária , Parada Cardíaca Induzida/métodos , Idoso , Encéfalo/metabolismo , Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Temperatura Baixa , Feminino , Parada Cardíaca Induzida/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Estudos Prospectivos , TemperaturaRESUMO
Cryopreserved aortic allografts were used for aortic valve replacement in 80 patients between 1986 and 1994 (infracoronary in 46 and complete root replacement in 34). Hospital mortality was 6.3% (5/80) with all deaths occurring in the infracoronary group. Three of five deaths were in patients with endocarditis and valve ring abscess. Left ventricular-aortic mean pressure gradients across the allograft valves were significantly lower for root replacement patients (mean, 9.0 +/- 6.9 mm Hg versus 18.1 +/- 8.7 mm Hg for infracoronary patients) (p = 0.0001). No patient having root allograft replacement had early echocardiographic aortic insufficiency greater than grade 1 versus 28% of those having infracoronary implantations. Late aortic insufficiency of grade 2 or greater was seen in 46% of patients having infracoronary implantation versus 17% of patients having root implantation. Nine patients had explantation of an aortic allograft (eight infracoronary and one root). Reasons for explantation were as follows: endocarditis (three infracoronary, one root), technical (three infracoronary), undiagnosed idiopathic hypertrophic subaortic stenosis (1 patient), and prolapsing infracoronary leaflet (1 patient). Actuarial freedom from grade 3 and 4 aortic insufficiency or explantation was 77% at 7 years for infracoronary implantations. We conclude that the infracoronary aortic allograft has an unacceptable frequency of late insufficiency and its use in this position should be abandoned. The substantial incidence of late endocarditis in the infracoronary (free-hand) aortic allograft was surprising.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/transplante , Análise Atuarial , Adulto , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Causas de Morte , Intervalo Livre de Doença , Ecocardiografia Doppler em Cores , Feminino , Seguimentos , Hemodinâmica , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Transplante Homólogo/métodosRESUMO
Transesophageal echocardiography (TEE) offers spectacularly detailed images of thoracic aortic anatomy and blood flow; however, its utility for diagnosis of aortic trauma is unknown. Our case underscores the ability of TEE to diagnose aortic transection. The speed, mobility, and accuracy of TEE makes it an attractive means of diagnosing aortic trauma in the critically ill.
Assuntos
Ruptura Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Idoso , Aorta Torácica/diagnóstico por imagem , Feminino , HumanosRESUMO
Refinements in vascular surgery have made repair of arterial injuries common throughout the world. There seems to be little doubt among trauma surgeons that primary repair of arterial injuries is the method of choice, as long as there is little devitalized arterial tissue and the procedure can be accomplished without tension on the suture lines or stenosis at the repair. When a lateral repair or primary anastomosis is not feasible, the type of conduit to be used is still the subject of controversy. Most clinical reports within the past 30 years state that autogenous vein is the grafting material of choice in traumatic wounds. However, the most recent investigations of the data do not favor autogenous vein grafts and, in fact, may lean toward prosthetic materials as the most satisfactory conduits for repairing traumatized arteries.
Assuntos
Bioprótese , Prótese Vascular , Vasos Sanguíneos/lesões , Materiais Biocompatíveis , Humanos , Polietilenotereftalatos , Politetrafluoretileno , Veia Safena/transplanteAssuntos
Biguanidas/farmacologia , Proteus/efeitos dos fármacos , Antibacterianos/farmacologia , Anti-Infecciosos Urinários/farmacologia , Bacteriúria , Resistência Microbiana a Medicamentos , Humanos , Ácido Nalidíxico/farmacologia , Proteus/isolamento & purificação , Infecções Urinárias/microbiologiaRESUMO
OBJECTIVE: To compare the effects of milrinone versus epinephrine administered after cardiopulmonary bypass (CPB) on left ventricular compliance. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting adult patients. INTERVENTIONS: Patients undergoing aortocoronary bypass surgery were randomized to receive 50 microg/kg of milrinone (group M; n = 10) or 0.03 microg/kg/min of epinephrine (group E; n = 10) shortly after separation from CPB. Left ventricular compliance was assessed by observing changes in left ventricular end-diastolic area (LVEDA) in the short-axis view with transesophageal echocardiography, while maintaining a constant left atrial pressure. Measurements were performed (1) before CPB, (2) after separation from CPB, and (3) after either milrinone or epinephrine. MEASUREMENTS AND MAIN RESULTS: Baseline LVEDA decreased by 20% after CPB in the milrinone group (from 16.6 +/- 3.1 cm2 to 14.3 +/- 2.4 cm2; p < 0.05) and by 22% in the epinephrine group (from 19.4 +/- 4.1 cm2 to 17.2 +/- 3.8 cm2; p < 0.05). LVEDA increased by 15% after milrinone (from 14.3 +/- 2.4 cm2 to 15.6 +/- 2.8 cm2; p < 0.05) but remained unchanged after epinephrine (from 17.2 +/- 3.8 cm2 to 17.1 +/- 4.2 cm2; p = ns). CONCLUSIONS: Left ventricular compliance was decreased after CPB. The administration of milrinone, but not epinephrine, was associated with a partial return to prebypass values. The exact mechanism of action remains to be determined.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Ponte Cardiopulmonar , Cardiotônicos/uso terapêutico , Epinefrina/uso terapêutico , Milrinona/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Complacência (Medida de Distensibilidade) , Ponte de Artéria Coronária , Ecocardiografia Transesofagiana , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , MasculinoRESUMO
OBJECTIVES: To compare changes in blood flow in a grafted internal mammary artery (IMA) after cardiopulmonary bypass (CPB) in response to the administration of milrinone or nitroglycerin and to establish the effects of alpha-adrenergic stimulation. DESIGN: Randomized study. SETTING: A university medical center hospital and a Veterans Affairs Medical Center hospital. PARTICIPANTS: Thirty consenting adults scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomized to receive a 2 microg/kg/min infusion of nitroglycerin (n = 10), a loading dose of 50 microg/kg of milrinone (n = 10), or both drugs combined (n = 10) shortly after CPB. Intravenous phenylephrine was administered to increase mean arterial pressure by 20%. IMA flow was measured with a calibrated laser Doppler flow probe. Hemodynamic and flow measurements were obtained before and after every intervention. MEASUREMENTS AND MAIN RESULTS: Nitroglycerin and milrinone increased mean IMA flow, but the increase was greater with milrinone. Both drugs combined were superior to nitroglycerin alone but not to milrinone. The addition of phenylephrine to nitroglycerin increased IMA flow in 6 of 10 patients. IMA flow decreased in 4 of 10 patients, however. Phenylephrine significantly increased IMA blood flow in patients receiving milrinone or in those given both drugs combined. CONCLUSION: After CPB, milrinone and nitroglycerin vasodilate the IMA; however, the combination of both drugs was not superior to milrinone alone. When using alpha-adrenergic stimulation, milrinone proved superior to nitroglycerin in preserving IMA flow.
Assuntos
Velocidade do Fluxo Sanguíneo , Ponte Cardiopulmonar , Anastomose de Artéria Torácica Interna-Coronária , Artéria Torácica Interna/efeitos dos fármacos , Milrinona/administração & dosagem , Nitroglicerina/administração & dosagem , Inibidores de Fosfodiesterase/administração & dosagem , Vasodilatadores/administração & dosagem , Agonistas alfa-Adrenérgicos/farmacologia , Quimioterapia Combinada , Hemodinâmica/efeitos dos fármacos , Humanos , Artéria Torácica Interna/diagnóstico por imagem , Artéria Torácica Interna/fisiologia , Fenilefrina/farmacologia , Ultrassonografia , Vasodilatação/efeitos dos fármacosRESUMO
Stable plasmid-driven expression of the liver-specific gene product cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) was used to alter the cellular content of transcriptionally active sterol response element binding protein 1 (SREBP1). As a result of stable expression of 7alpha-hydroxylase, individual single cell clones expressed varying amounts of mature SREBP1 protein. These single cell clones provided an opportunity to identify SREBP1-regulated genes that may influence the assembly and secretion of apoB-containing lipoproteins. Our results show that in McArdle rat hepatoma cells, which normally do not express 7alpha-hydroxylase, plasmid-driven expression of 7alpha-hydroxylase results in the following: 1) a linear relationship between (i) the cellular content of mature SREBP1 and 7alpha-hydroxylase protein, (ii) the relative expression of 7alpha-hydroxylase mRNA and the mRNA's encoding the enzymes regulating fatty acid, i.e. acetyl-CoA carboxylase and sterol synthesis, i.e. HMG-CoA reductase, (iii) the relative expression of 7alpha-hydroxylase mRNA and microsomal triglyceride transfer protein mRNA, a gene product that is essential for the assembly and secretion of apoB-containing lipoproteins; 2) increased synthesis of all lipoprotein lipids (cholesterol, cholesterol esters, triglycerides, and phospholipids); and 3) increased secretion of apoB100 without any change in apoB mRNA. Cells expressing 7alpha-hydroxylase contained significantly less cholesterol (both free and esterified). The increased cellular content of mature SREBP1 and increased secretion of apoB100 were concomitantly reversed by 25-hydroxycholesterol, suggesting that the content of mature SREBP1, known to be decreased by 25-hydroxycholesterol, mediates the changes in the lipoprotein assembly and secretion pathway that are caused by 7alpha-hydroxylase. These data suggest that several steps in the assembly and secretion of apoB-containing lipoproteins by McArdle hepatoma cells may be coordinately linked through the cellular content of mature SREBP1.
Assuntos
Apolipoproteínas B/metabolismo , Hidrocarboneto de Aril Hidroxilases , Proteínas Estimuladoras de Ligação a CCAAT , Proteínas de Ligação a DNA/fisiologia , Lipídeos/biossíntese , Proteínas Nucleares/fisiologia , Fatores de Transcrição , Acetil-CoA Carboxilase/genética , Animais , Sistema Enzimático do Citocromo P-450/análise , Sistema Enzimático do Citocromo P-450/genética , Hidroximetilglutaril-CoA Redutases/genética , Lipoproteínas VLDL/biossíntese , RNA Mensageiro/análise , Ratos , Esteroide Hidroxilases/análise , Esteroide Hidroxilases/genética , Proteína de Ligação a Elemento Regulador de Esterol 1RESUMO
Mechanisms of protective immunity to mycobacterial infection in the lung remain poorly defined. In this study, T-cell subset expansion and cytokine expression in bronchoalveolar spaces, lung parenchyma, and mediastinal lymph nodes of mice infected intratracheally with Mycobacterium bovis-Calmette-Guerin bacillus (BCG) were analyzed in parallel with histopathology and bacterial burden. M. bovis-BCG was cleared rapidly from bronchoalveolar spaces without evidence for persistence. In lung parenchyma bacteria grew during the first 4 wk followed by gradual clearance with less than 0.1% of the original inoculum persisting for more than 8 mo. Clearance of M. bovis-BCG from bronchoalveolar lavage was associated with recruitment of both neutrophils and lymphocytes. Lung CD4(+), CD8(+), and gammadelta T-cell receptor-positive T cells expanded maximally by Week 4, and declined by Week 8 to control values despite bacterial persistence. Both CD4(+) and CD8(+) lung T cells produced interferon (IFN)-gamma in response to M. bovis-BCG. Four distinct pathologic states of lung parenchymal infection were noted. Early focal sub-bronchial inflammation with transmigration of cells into airways was followed by diffuse peribronchitis, perivasculitis, and alveolitis with activated macrophages, lymphoblasts, and occasional giant cells. The latter stage corresponded to maximal M. bovis-BCG growth. Resolving infection consisted of small lymphocytes and foamy macrophages, which coincided with decreasing M. bovis-BCG colony-forming units, T-cell infiltration, and IFN-gamma expression. A final quiescent phase consisted of residual lymphoid aggregates and perivasculitis associated with persistent spontaneous IFN-gamma production. Bacterial dissemination to lymph node and spleen occurred by Week 4 and declined in parallel to lung. In contrast to lung, IFN-gamma secretion was detected only late despite early expansion of CD4(+) and CD8(+) T cells. By reverse transcriptase/polymerase chain reaction, IFN-gamma and interleukin (IL)-12 p40 messenger RNA (mRNA) in lung paralleled IFN-gamma protein production. Tumor necrosis factor-alpha, IL-4 and IL-10 mRNA expression was not increased during M. bovis-BCG lung infection. Thus, protective immunity to M. bovis-BCG in the lung evolved differently in air space, lung, and lymph node.
Assuntos
Pulmão/imunologia , Mycobacterium bovis/imunologia , Tuberculose Pulmonar/imunologia , Animais , Anticorpos Antibacterianos , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Linfócitos T CD4-Positivos/química , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/química , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/microbiologia , Feminino , Expressão Gênica/imunologia , Interferon gama/genética , Interferon gama/imunologia , Intubação Intratraqueal , Pulmão/microbiologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/microbiologia , Linfonodos/patologia , Mediastino , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium bovis/crescimento & desenvolvimento , RNA Mensageiro/análise , Receptores de Antígenos de Linfócitos T gama-delta/análise , Organismos Livres de Patógenos Específicos , Baço/imunologia , Baço/microbiologia , Baço/patologia , Tuberculose Pulmonar/patologiaRESUMO
OBJECTIVE: To examine the effects of calcium chloride (CaCl2) administration on blood flow through the grafted left internal mammary artery (IMA) after cardiopulmonary bypass (CPB). DESIGN: Single-arm prospective study. SETTING: University-affiliated hospital operating room. PARTICIPANTS: Twenty adult patients scheduled for coronary artery bypass graft surgery with IMA graft. INTERVENTIONS: IMA flow was measured noninvasively with a laser Doppler flow probe placed around the IMA, and measurements were recorded for 10 seconds and averaged. After separation from CPB under stable hemodynamics, baseline IMA flow was measured. CaCl2, 15 mg/kg, was administered intravenously over 1 minute. Blood pressure, left atrial pressure, heart rate, and IMA flow were then measured at 1, 5, and 10 minutes. Coronary perfusion pressure and IMA vascular resistance were calculated. MEASUREMENTS AND MAIN RESULTS: After CaCl2 administration, IMA blood flow significantly decreased from baseline at 1, 5, and 10 minutes (from 28+/-9 mL/min to 19+/-8 mL/min, 22+/-6 mL/min, and 25+/-4 mL/min), with gradual return toward baseline over time. Blood pressure, coronary perfusion pressure, and IMA vascular resistance significantly increased at 1 and 5 minutes after CaCl2. Left atrial pressure and heart rate remained unchanged. No systolic regional wall motion abnormalities were detected on transesophageal echocardiography. CONCLUSIONS: CaCl2, administered as a bolus dose after separation from CPB, transiently but significantly reduces IMA flow and can potentially trigger vasospasm, increasing the risk for myocardial ischemia or infarction in susceptible patients. Further studies are needed to determine whether this effect also occurs with nitrosodilators or phosphodiesterase inhibitors.
Assuntos
Cloreto de Cálcio/efeitos adversos , Ponte Cardiopulmonar , Ponte de Artéria Coronária , Artéria Torácica Interna/efeitos dos fármacos , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Cloreto de Cálcio/administração & dosagem , Circulação Coronária/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Fluxometria por Laser-Doppler , Masculino , Artéria Torácica Interna/fisiologia , Artéria Torácica Interna/transplante , Estudos Prospectivos , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosRESUMO
OBJECTIVE: To compare changes on grafted internal mammary artery (IMA) flow after cardiopulmonary bypass in response to the administration of milrinone or epinephrine. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting, adult patients undergoing CABG. INTERVENTIONS: Patients were randomized to receive either milrinone, 50 microg/kg, or epinephrine, 0.03 microg/kg/min, immediately after cardiopulmonary bypass. IMA flow was measured with a laser Doppler flow probe before and after the administration of either drug. MEASUREMENTS AND MAIN RESULTS: Baseline grafted IMA flow was similar for both groups (milrinone, 38+/-14 mL/min; epinephrine, 33+/-10 mL/min). In patients who received milrinone, flow increased by 24% to 50+/-17 mL/min, p<0.05; whereas with epinephrine, it remained essentially unchanged (33+/-10 v. 31+/-11 mL/min). CONCLUSIONS: This study confirms that the vasodilatory effect of milrinone on the IMA is also present after its anastomosis, whereas low-dose epinephrine exhibits neither beneficial nor adverse effects. It is suggested that in the absence of excessive vasodilation, milrinone should be considered as a first-line inotrope after coronary artery bypass graft surgery, to achieve an increase in contractility and IMA artery flow.
Assuntos
Ponte Cardiopulmonar , Cardiotônicos/farmacologia , Ponte de Artéria Coronária , Epinefrina/farmacologia , Artéria Torácica Interna/efeitos dos fármacos , Milrinona/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Vasodilatadores/farmacologia , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Fluxometria por Laser-Doppler , Masculino , Artéria Torácica Interna/transplante , Contração Miocárdica/efeitos dos fármacos , Estudos ProspectivosRESUMO
Although neutrophils have been identified as sources of inflammatory cytokines and chemokines, little is known about their immunologic function during mycobacterial infection in the lungs. In this study, we examined the growth of Mycobacterium bovis BCG in the lungs under experimental conditions that altered neutrophil recruitment to the lungs. Depletion and recruitment of neutrophils was associated with respective increases and decreases in M. bovis BCG growth. Thus, neutrophils may enhance mycobacteriocidal immunity in the lungs.