RESUMO
Continuous intrathecal Baclofen application (ITB) through an intracorporeal pump system is widely used in adults and children with spasticity of spinal and supraspinal origin. Currently, about 1200 new ITB pump systems are implanted in Germany each year. ITB is based on an interdisciplinary approach with neurologists, rehabilitation specialists, paediatricians and neurosurgeons. We are presenting the proceedings of a consensus meeting organised by IAB-Interdisciplinary Working Group for Movement Disorders. The ITB pump system consists of the implantable pump with its drug reservoir, the refill port, an additional side port and a flexible catheter. Non-programmable pumps drive the Baclofen flow by the reservoir pressure. Programmable pumps additionally contain a radiofrequency control unit, an electrical pump and a battery. They have major advantages during the dose-finding phase. ITB doses vary widely between 10 and 2000 µg/day. For spinal spasticity, they are typically in the order of 100-300 µg/day. Hereditary spastic paraplegia seems to require particularly low doses, while dystonia and brain injury require particularly high ones. Best effects are documented for tonic paraspasticity of spinal origin and the least effects for phasic muscle hyperactivity disorders of supraspinal origin. Oral antispastics are mainly effective in mild spasticity. Botulinum toxin is most effective in focal spasticity. Myotomies and denervation operations are restricted to selected cases of focal spasticity. Due to its wide-spread distribution within the cerebrospinal fluid, ITB can tackle wide-spread and severe spasticity.
Assuntos
Baclofeno/administração & dosagem , Transtornos dos Movimentos/tratamento farmacológico , Relaxantes Musculares Centrais/administração & dosagem , Espasticidade Muscular/tratamento farmacológico , Alemanha , Humanos , Bombas de Infusão Implantáveis/efeitos adversos , Injeções EspinhaisRESUMO
The findings of a large prospective study designed to identify primary and/or secondary haemostatic disorders before surgical interventions are presented. A total of 5649 unselected adult patients were enrolled to identify impaired haemostasis before surgical interventions. Each patient was asked to answer a standardized questionnaire concerning bleeding history. Activated partial thromboplastin time (aPTT), prothrombin time (PT), and platelet counts (PC) including PFA-100 (platelet function analyzer): collagen-epinephrine (C/E), and collagen-ADP (C/ADP) were routinely done in all patients. Additional tests, bleeding time (BT), von Willebrand factor (VWF:Ag, VWF:Rcof) and a further haemostaseological diagnostic was performed only in patients with a positive bleeding history and/or evidence of impaired haemostasis; e.g., drug ingestion. The bleeding history was negative in 5021 patients (88.8%) but positive in the remaining 628 (11.2%). Impaired haemostasis could be verified only in 256 (40.8%) of these patients. The vast majority was identified with PFA-100: C/E (n = 250; 97.7%). The sensitivity of the PFA-100: collagen-epinephrine was the highest (90.8%) in comparison to the other screening tests (BT, aPTT, PT, VWF : Ag). The positive predictive value (to detection of impaired haemostasis) of the PFA-100: collagen-epinephrine with the standardized questionnaire was high (82%), but the negative predictive value was higher (93%). The use of a standardized questionnaire and, if indicated, the PFA-100: C/E and/or other specific tests not only ensure the detection of impaired haemostasis in almost every case but also a significant reduction of the costs. Based on these data, national regards are formulated or under construction.
Assuntos
Transtornos Hemostáticos/diagnóstico , Cuidados Pré-Operatórios , Difosfato de Adenosina/farmacologia , Tempo de Sangramento , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Colágeno/farmacologia , Epinefrina/farmacologia , Transtornos Hemostáticos/sangue , Humanos , Ativação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Tempo de Protrombina , Inquéritos e QuestionáriosRESUMO
The aim of this study was to compare and evaluate the ability of near infrared- (NIR), Raman- and attenuated-total-reflection infrared (ATR-IR) spectroscopy as tools for the identification of washing powder brands as well as for an overall quantitative analysis of all ingredients of the analyzed laundry detergents. The laundry detergents used in this work were composed of 22 different ingredients. For this purpose, principal component analysis (PCA) cluster models and partial least-squares (PLS) regression models were developed and different data pre-processing algorithms such as standard-normal-variate (SNV), multiplicative scatter correction (MSC), first derivative BCAP (db1), second derivative smoothing (ds2), smoothing Savitzky Golay 9 points (sg9) as well as different normalization procedures such as normalization between 0 and 1 (n01), normalization unit length (nle) or normalization by closure (ncl) were applied to reduce the influence of systematic disturbances. The performance of the methods was evaluated by comparison of the number of principal components (PCs), regression coefficient (r), Bias, Standard error of prediction (SEP), ratio performance deviation (RPD) and range error ratio (RER) for each calibration model. For each of the 22 ingredients separate calibration models were developed. Raman spectroscopy was suitable for the analysis of only two ingredients (dye transfer inhibitor 1 and surfactant 6) and it was not possible to record all Raman spectra due to high fluorescence. NIR and ATR-IR are powerful methods to analyze washing detergents with low numbers of PCs being necessary, regression coefficients of only little below 1, small Biases and SEPs compared to the range and high RPDs and RERs.
RESUMO
The measurement of the degree of oxidative stress in patients often causes problems because of the lack of useful parameters. Therefore, we used an ELISA technique to evaluate serum protein carbonyls as a parameter of oxidative stress in patients during coronary heart surgery. Protein carbonyls were detected in serum samples of 14 patients undergoing coronary surgery and cardiopulmonary artery bypass grafting. A clear 2- to 3-fold increase in protein carbonyls in serum samples taken from human venous coronary sinus could be detected in the reperfusion period of the heart. We compared these data with markers of oxidative stress previously used, such as the glutathione status and the lipid peroxidation product malondialdehyde (MDA). Strong correlations of the protein carbonyl formation with MDA (r2 = 0.86) and oxidized glutathione (r2 = 0.81) were found in the early reperfusion stage. Increased levels of oxidized glutathione and MDA were detected only in the early reperfusion period. In contrast, the serum protein carbonyl content remained elevated for several hours, indicating a considerably slower serum clearance of oxidized proteins compared with that of lipid peroxidation products and the normalization of the glutathione status. We therefore concluded that the measurement of serum carbonyls by this ELISA technique is suitable to detect oxidative stress in serum samples of patients. The relative stability of the parameter makes the protein carbonyl detection even more valuable for clinical purposes.
Assuntos
Proteínas Sanguíneas/metabolismo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Idoso , Biomarcadores/sangue , Ponte Cardiopulmonar/efeitos adversos , Glutationa/sangue , Humanos , Malondialdeído/sangue , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/etiologia , Oxirredução , Estresse OxidativoRESUMO
The referral of critically ill cancer patients to an intensive care unit (ICU) is a matter of controversial debate. This study was conducted by an interdisciplinary clinical group to evaluate the outcome of ICU treatment in cancer patients according to their characteristics at the time of referral. A retrospective analysis was used to identify relevant subgroups among 189 consecutive cancer patients referred as emergencies to one of four ICUs during a 2-year period. Reasons for ICU referral were pneumonia (29.6%), sepsis (27.0%), fungal infection (11.1%), another infection (9.5%), gastrointestinal emergency (16.9%), treatment-related organ toxicity (6.9%), or other, non-infectious complications (43.9%). Vasopressor support was required in 50.3%, mechanical ventilation in 49.7%, and haemodialysis/-filtration in 26.5% of the patients. Overall, 41.3% died during ICU treatment, 12.2% died after transfer from ICU to a non-ICU ward, and 35.4% were discharged alive. Sepsis, mechanical ventilation, vasopressor support, renal replacement therapy and neutropenia were independent risk factors for fatal outcome, but no single risk factor unequivocally predicted death. All patients with fungal infection who required vasopressor support and either had sepsis (n=13) or needed mechanical ventilation (n=14) died during ICU treatment, while all non-septic patients. who did not require mechanical ventilation, were younger than 74 years of age and had a non-infectious underlying complication (n=29), survived. This analysis may help to early identify relevant subgroups of cancer patients with different prognoses under ICU treatment. A prospective study to confirm the predictive usefulness of this approach is needed. Cancer patients should not be excluded from referral to the intensive care unit in an emergency solely due to their underlying malignant disease or a single unfavourable prognostic factor.
Assuntos
Cuidados Críticos , Neoplasias/terapia , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Árvores de Decisões , Emergências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/terapia , Neutropenia/terapia , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Fatores de Risco , Sepse/terapia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Expression of exogenous DNA or small interfering RNA (siRNA) in vitro is significantly affected by the particular delivery system utilized. In this study, we evaluated the transfection efficiency of plasmid DNA and siRNA into human brain microvascular endothelial cells (HBMEC) and meningioma cells, which constitute the blood-cerebrospinal fluid barrier, a target of meningitis-causing pathogens. Chemical transfection methods and various lipofection reagents including Lipofectamin™, FuGene™, or jetPRIME®, as well as physical transfection methods and electroporation techniques were applied. To monitor the transfection efficiencies, HBMEC and meningioma cells were transfected with the reporter plasmid pTagGFP2-actin vector, and efficiency of transfection was estimated by fluorescence microscopy and flow cytometry. We established protocols based on electroporation using Cell Line Nucleofector® Kit V with the Amaxa® Nucleofector® II system from Lonza and the Neon® Transfection system from Invitrogen resulting in up to 41 and 82% green fluorescent protein-positive HBMEC, respectively. Optimal transfection solutions, pulse programs and length were evaluated. We furthermore demonstrated that lipofection is an efficient method to transfect meningioma cells with a transfection efficiency of about 81%. Finally, we applied the successful electroporation protocols to deliver synthetic siRNA to HBMEC and analyzed the role of the actin-binding protein cortactin in Neisseria meningitidis pathogenesis.
Assuntos
Encéfalo/metabolismo , DNA/administração & dosagem , Células Endoteliais/patologia , Plasmídeos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Transfecção/métodos , Aderência Bacteriana , Encéfalo/patologia , Forma Celular , Sobrevivência Celular , Cortactina/genética , Cortactina/metabolismo , DNA/genética , Eletroporação/métodos , Células Endoteliais/metabolismo , Citometria de Fluxo , Técnicas de Transferência de Genes , Genes Reporter , Células HEK293 , Células HeLa , Humanos , Lipídeos/química , Meningioma/metabolismo , Meningioma/patologia , Plasmídeos/genética , Interferência de RNA , RNA Interferente Pequeno/genéticaAssuntos
Pressão Sanguínea , Circulação Hepática , Transplante de Fígado/métodos , Transplante de Fígado/fisiologia , Circulação Extracorpórea , Feminino , Veia Femoral , Humanos , Rim/irrigação sanguínea , Rim/fisiologia , Masculino , Veia Porta , Estudos Prospectivos , Análise de Regressão , Veia SubcláviaRESUMO
UNLABELLED: During a period of 2.5 years self-healing coecostomies according to Stelzner (1970) were applied in 48 elective procedures to the left colon. The following operations were done by 16 different surgeons: left side hemicolectomy 5, sigma resection 24, anterior resection of the rectum 19, 13 of which had anastomoses less than 8 cm. RESULTS: Mean postoperative hospital care 25.3 days, no clinical manifestation of anastomotic leaks, first passing of stool after a mean of 8.5 days. Lethality of 4.2% independent of anastomoses, spontaneous occlusion of fistulae after 42 +/- 26 days. 21% local not life-endangering complications occurred.
Assuntos
Ceco/cirurgia , Doenças do Colo/cirurgia , Colostomia , Doenças Retais/cirurgia , Humanos , Complicações Pós-Operatórias/prevenção & controle , Próteses e Implantes , Deiscência da Ferida Operatória/prevenção & controle , CicatrizaçãoRESUMO
By means of long-term follow-ups of large numbers of patients it has been established that nitrogen cryotherapy for lid basaliomas produces very good results with regard to the cure rate, as well as having considerable advantages over other treatment methods. In contrast to other authors we did not employ the spray method, but a very high-performance nitrogen cryo unit with a closed probe. Experimental measurements showed that this unit is capable of generating at least the same temperatures as with the spray method. The cryoapplication technique is described. The cure rate and causes of recurrence in the first series in the total of 84 patients treated from 1979 to 1983 were evaluated by long-term follow-up. If cryobiological principles are observed and the recommended application technique is adhered to, the same cure rate can be achieved as with the spray method and other forms of treatment. There are considerable functional and cosmetic advantages, also as regards the patency of the lacrimal ducts.
Assuntos
Carcinoma Basocelular/cirurgia , Criocirurgia , Neoplasias Palpebrais/cirurgia , Carcinoma Basocelular/patologia , Neoplasias Palpebrais/patologia , Pálpebras/patologia , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , CicatrizaçãoRESUMO
Brain death is associated with loss of hypothalamic, pituitary and brain stem function resulting in apnea, bradycardia and hypotension, poikilothermia, and diabetes insipidus. In order to preserve body functions mechanical ventilation is continued with the aim to maintain an arterial partial pressure of oxygen of more than 100 mmHg. Previous fluid restrictions and the application of diuretics during the treatment of high intracranial pressure frequently result in dehydration. Progressive vasodilation may induce severe hypotension and fluid replacement with cristalloids and if necessary colloids may be called for until the central venous pressure reaches 10 cm H2O. Continuous substitution of potassium and the use of hypotonic solutions such as glucose 5% may avoid hypokalaemia and hypernatraemia, respectively. Inotropic support with dopamine (5-10 micrograms/kg.min) or adrenaline (0.01-0.1 micrograms/kg.min) may be needed to maintain normal mean arterial blood pressure (65 mmHg). Polyuria (5000 ml/24 h) can be treated by continuous intravenous infusion of antidiuretic hormone (0.5-2-10 U/h). Hypothermia must be prevented by warming all fluids (37 degrees C) and covering the patient with heat saving blankets.
Assuntos
Morte Encefálica/fisiopatologia , Cuidados para Prolongar a Vida/métodos , Transplante de Órgãos/fisiologia , Doadores de Tecidos , Alemanha , Humanos , Monitorização Fisiológica , Preservação de Órgãos/métodos , Doadores de Tecidos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/legislação & jurisprudênciaRESUMO
In a prospective study, the complications of 1071 patients scheduled for thoracic epidural catheterization for postoperative analgesia (TEA) were studied. All catheters were inserted preoperatively between segment Th 2/3 and Th 11/12 under local anesthesia. Balanced anesthesia with endotracheal intubation and TEA were combined. Postoperatively 389 patients (36.9%) were monitored on a normal surgical ward. Buprenorphine, 0.15 to 0.3 mg, and if needed bupivacaine 0.375% 3-5 ml h-1 were given epidurally. Primary perforation of the dura occurred in 13 patients (1.23%). Radicular pain syndromes were observed in six patients (0.56%). In one patient (0.09%) respiratory depression was seen in close connection with the epidural administration of 0.3 mg buprenorphine. Although 116 patients (10.83%) showed one abnormal clotting parameter but no clinical signs of hemorrhage, there was no complication related to this group. No persisting neurological sequelae caused by the thoracic epidural catheters were found. In conclusion, continuous TEA with buprenorphine for postoperative pain relief after major abdominal surgery is a safe method without too high a risk of catheter-related or drug-induced complications, even on a normal surgical ward and when one clotting parameter is abnormal.
Assuntos
Analgesia Epidural/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgesia Epidural/instrumentação , Analgesia Epidural/métodos , Anestesia Intravenosa , Transtornos da Coagulação Sanguínea/fisiopatologia , Bupivacaína/administração & dosagem , Buprenorfina/administração & dosagem , Dura-Máter/lesões , Etidocaína/administração & dosagem , Feminino , Fentanila , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Transtornos de Sensação/etiologia , Vértebras Torácicas , Fatores de TempoRESUMO
Upper abdominal and thoracic surgeries require efficient pain management. The complications of postoperative analgesia include respiratory depression and--when choosing the epidural route--possible damage to the spinal cord by infection, trauma, or bleeding. Therefore, thoracic epidural analgesia may appear to be too risky and is frequently cancelled although many studies have shown its excellent efficacy. Controlled studies comparing thoracic epidural analgesia to lumbar epidural analgesia or intravenous analgetic regimens with special regard to the patient's outcome are contradictory. To make the preoperative decision on the method of pain control more rational, we studied catheter-related complications from 2056 thoracic epidural catheters used for intra- and postoperative analgesia retrospectively (n = 1002) and prospectively (n = 1054) over a 5 1/2-year period. In all patients the thoracic epidural catheter was inserted preoperatively using local anaesthesia, in most cases by the paramedian approach between level T 5/6 and T 8/9. During the clinical course of all patients there were no clinical signs of any epidural bleeding or infection. Neurological complications caused by the epidural catheter did not occur. Seven patients (0.035%) experienced radicular pain that disappeared after removal of the catheter or interruption of the puncture, respectively. A primary perforation of the dura mater was noticed in 0.5% of cases retrospectively and 1.23% prospectively. Respiratory depression following epidural application of 0.3 mg buprenorphine was seen in 1 patient (0.05%). Continuous analgesia with local anaesthetics and/or opioids applied epidurally by a thoracic catheter was performed on the peripheral ward (n = 829, 40%) if close monitoring of the neurological status as well as rapid diagnosis of any painful paraesthesia or paraplegia was possible.
Assuntos
Abdome/cirurgia , Anestesia Epidural/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo/efeitos adversos , Depressão Química , Humanos , Vértebras Lombares , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração/efeitos dos fármacos , Estudos Retrospectivos , Vértebras TorácicasRESUMO
The routine use of veno-venous bypass during the anhepatic phase of orthotopic liver transplantation is controversial. Decreased shunt flows (1.5-3.0 litre min-1), as reported in the literature, may explain the lack of beneficial effects on outcome. We have studied the influence of bypass flows on caval pressure gradient (CPG) and renal perfusion pressure (RPP) in 45 patients undergoing orthotopic liver transplantation using a portofemoro-subclavian veno-venous bypass system. Mean shunt flow was 3.63 litre min-1. Second-order polynomial regressions best described the relationship between shunt flow and CPG (r = 0.674), RPP (r = 0.727), and cardiac output (r = 0.602). Shunt flows less than 3.0 litre min-1 failed to normalize CPG and RPP, whereas flows greater than 5.0 litre min-1 did not substantially improve haemodynamic state.
Assuntos
Pressão Sanguínea/fisiologia , Transplante de Fígado/fisiologia , Adulto , Débito Cardíaco/fisiologia , Feminino , Veia Femoral/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Veia Subclávia/fisiologia , Veias Cavas/fisiologiaRESUMO
OBJECTIVE: During cardiopulmonary bypass, inflammation and immunosuppression is present. We measured circulating mediators and monocyte-based functions and tested the hypothesis that these variables are influenced by methylprednisolone (MP) or tirilazad mesylate (TM) treatment. DESIGN: Randomized, controlled, double-blind prospective trial. SETTING: A university hospital. PATIENTS: Thirty-nine patients scheduled for conventional coronary surgery with three-vessel disease. INTERVENTIONS: Preoperative application of MP (15 mg/kg) or TM (10 mg/kg) compared with placebo (PL). MEASUREMENTS AND MAIN RESULTS: Circulating proinflammatory markers including interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and C-reactive protein were all decreased by MP treatment but not by TM treatment. Whereas rapid increases in circulating anti-inflammatory IL-10 were superinduced by MP but not TM, plasma levels of IL-1RA and transforming growth factor beta were not altered by either treatment. Decreased ex vivo lipopolysaccharide-stimulated secretion of tumor necrosis factor alpha was prolonged after MP treatment but not after TM treatment. Perioperative stimulated secretion of IL-12 and interferon gamma was diminished in all groups, whereas ex vivo IL-1RA secretion tended to increase in all groups. Depression of monocyte surface expression of HLA-DR was significantly greater in patients treated with MP, whereas CD14 expression did not change. CONCLUSIONS: These data confirm that, during cardiopulmonary bypass, pro- and anti-inflammatory systems are activated at the same time, whereas monocyte-based immune functions are depressed. Treatment with MP abrogates proinflammatory mediators and induces a shift toward anti-inflammation at the cost of further functional monocyte deficits, whereas treatment with TM apparently has neither anti-inflammatory nor immunosuppressive actions in this setting.
Assuntos
Antioxidantes/uso terapêutico , Ponte Cardiopulmonar , Glucocorticoides/uso terapêutico , Terapia de Imunossupressão , Inflamação/tratamento farmacológico , Metilprednisolona/uso terapêutico , Pregnatrienos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Interleucinas/sangue , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Veno-venous bypass is commonly used during orthotopic liver transplantation, but there is some controversy as to whether it contributes to a better outcome. Low shunt flows frequently reduce the efficacy of portofemoro-axillary systems and so a percutaneous cannulation technique for the subclavian and femoral vein with large bore catheters was developed in order to facilitate bypass management. This study reports the performance and complications of a portofemoro-subclavian bypass system during the anhepatic phase of human orthotopic liver transplantation in 85 patients. A percutaneous cannulation technique and two 7 mm (subclavian and femoral) catheters, inserted pre-operatively, were used in a pump driven portofemoro-subclavian bypass system. Coagulation profiles, shunt flows, haemodynamic parameters, and peri-operative complications associated with bypass were recorded for each patient. Percutaneous cannulation of the left femoral and subclavian vein was successful in 78 patients (91.8%). Mean femoro-subclavian shunt flow was 1.45 l.min-1 (SD 0.37), and mean portofemoro-subclavian flow was 4.28 l.min-1 (SD 1.03). Although oxygen delivery was not maintained at pre-shunt levels (559.7 (SD 147) vs 506 (SD 107) ml.min-1.m-2, p < 0.05) renal perfusion pressure stayed above 50 mmHg (during shunt it was 56 (SD 9) mmHg). One intra-operative air embolism was observed (1.2%), and in one patient a myocardial infarction occurred during the anhepatic phase; neither complication was considered to be related to the percutaneous cannulation technique. There were no bleeding complications. After operation, all chest X rays were normal and clinical examination revealed no adverse effects of portofemoro-subclavian bypass.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cateterismo Venoso Central/métodos , Veia Femoral , Transplante de Fígado/métodos , Veia Subclávia , Adulto , Coagulação Sanguínea , Cateterismo Venoso Central/efeitos adversos , Feminino , Hemodinâmica , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , PunçõesRESUMO
OBJECTIVE: During the last decade, experimental and clinical evidence has accumulated that antithrombin (AT) exerts anti-inflammatory effects when given in high doses. Meanwhile, AT substitution has been shown to significantly increase prostacyclin release. However, the link between endothelial AT binding and anti-inflammatory AT effects remains to be established in vivo, although heparin has been shown to counteract anti-inflammatory AT effects. We hypothesized that the administration of heparin in endotoxin-challenged rats would decrease endothelial AT binding and systemic prostacyclin concentrations. DESIGN: Prospective, randomized, controlled experimental in vivo study. SETTING: Research laboratory of a university hospital. ANIMALS: Fifty-six Wistar rats. INTERVENTIONS: Baseline values of coagulation variables were measured in six animals. Forty of 50 Wistar rats in the study groups were given endotoxin (50 mg x kg(-1) iv) and were treated with saline (group LPS), AT (15 units x kg(-1) x hr(-1)) (LPS+AT), AT and heparin (80 IU x kg(-1) x hr(-1)), or AT and hirudin (0.12 mg x kg(-1) x hr(-1)); the other 10 received saline instead of endotoxin and were treated with AT alone. Before endotoxin application, a tracheostomy was performed, and venous and arterial catheters were inserted for blood sampling and infusion. MEASUREMENTS: Intravital endothelial AT binding was studied by using fluorescence isothiocyanate-marked antibodies during intravital microscopy of intestinal submucosal venules. Systemic prostacyclin, thrombin-AT complex, and fibrinogen concentrations were measured after 4 hrs. Intergroup differences were tested by Kruskal-Wallis analysis of variance on ranks. MAIN RESULTS: AT and AT + heparin were equally effective in inhibiting systemic procoagulant turnover as reflected by fibrinogen concentrations. Only the administration of AT + hirudin significantly prevented fibrinogen consumption (p < .05). In contrast with all other treatments, the administration of heparin significantly reduced intravital endothelial AT binding (p < .05). However, prostacyclin concentrations were similarly increased in all endotoxin-challenged study groups irrespective of the anticoagulatory treatment. CONCLUSIONS: There is evidence that heparin in contrast with hirudin prevents AT from being bound to the endothelial cell surface in this experimental model. Under low-dose AT substitution, systemic prostacyclin concentrations do not depend on whether heparin or hirudin is used for thrombin inhibition. These results support the view that heparin may counteract anti-inflammatory AT effects by keeping AT away from its endothelial binding sites; however, the results question the view that decreased endothelial prostacyclin release is solely responsible.
Assuntos
Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Heparina/uso terapêutico , Terapia com Hirudina , Trombina/análise , Animais , Lipopolissacarídeos/administração & dosagem , Masculino , Estudos Prospectivos , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
UNLABELLED: The effect of normothermic (36.2 degrees C +/- 0.6 degree C) nonpulsatile cardiopulmonary bypass (CPB) on splanchnic (hepatic) blood flow (SBF), splanchnic oxygen transport (DO2spl) and oxygen consumption (VO2spl), splanchnic lactate uptake and gastric mucosal pH (pHi, gastric tonometry) was studied in 12 adults (New York Heart Association class II, ejection fraction > or = 0.4) undergoing coronary artery surgery. SBF was estimated with the constant-infusion indocyanine green (ICG) technique using a hepatic venous catheter. DO2spl, VO2spl, and splanchnic lactate uptake were calculated using the Fick principle after the induction of anesthesia, during aortic cross-clamping, after CPB, and 2 and 7 h after admission to the intensive care unit (ICU). SBF, DO2spl, and VO2spl did not decrease during CPB but increased after ICU admission, whereas pHi decreased 7 h after ICU admission. Initial ICG extraction was 0.78, which decreased to 0.54 during aortic clamping and remained low thereafter. The increased arterial blood lactate concentrations were not associated with a decreased splanchnic lactate uptake. We conclude that normothermic CPB is not associated with deterioration in the global intestinal oxygen supply. The increase of blood lactate levels and the decrease in ICG extraction, as well as in pHi, are consistent with a systemic inflammatory response to CPB. IMPLICATIONS: This study demonstrated that normothermic cardiopulmonary bypass (at flows > 2.4 L.min-1.m-2) was not associated with deterioration in global intestinal oxygen delivery, which suggests that increased blood lactate concentrations and decreased gastric mucosal pH and indocyanine green extraction are manifestations of a systemic inflammatory response to cardiopulmonary bypass.