RESUMO
A 73-year-old obese woman underwent coronary artery-bypass operation in 11/1995 because of a coronary two vessel disease. The left coronary artery was bypassed by the left mammarial internal artery. In 2 and 3/2002, balloon-dilatation of stenoses of the right coronary artery and the circumflex was performed. Angina pectoris relapsed and in 9/2002 the patient was admitted to our hospital with tentative diagnosis of restenosis. Physical investigation showed a blood pressure of the right arm of 160/80 and of the left arm of 120/ 80 mmHg. Coronarography showed the three vessel disease known since 2/2002 with a restenosis of the right coronary artery which was immediately treated by balloon-dilatation and stent-implantation. Colour duplex-sonography of the carotid and subclavian arteries revealed extraordinary plaques and a reduced flow of the left vertebral artery. The left subclavian artery could only be seen distal to the discharge of the vertebral artery and showed a poststenotic flow. The patient had angina pectoris when carrying out personal hygiene already 2 days after balloon-dilatation and stent-implantation. ECG showed new aspects. Coronarography showed no relapse of stenosis, but 70% stenosis of the left subclavian artery with a marked coronary-steal-syndrome. In 10/ 2002, the patient underwent balloon-dilatation and stent-implantation of the subclavian stenosis and became free of complaints. Coronary-steal-syndrome can be the reason for persistent angina pectoris in spite of successful coronary artery-bypass operation with a mammarial internal bypass. It is absolutely necessary to take blood pressure from both arms to recognise a possible stenosis of the subclavian artery which can be the key to all.
Assuntos
Angina Pectoris/diagnóstico , Angioplastia Coronária com Balão , Doença das Coronárias/cirurgia , Reestenose Coronária/diagnóstico , Revascularização Miocárdica , Complicações Pós-Operatórias/diagnóstico , Stents , Síndrome do Roubo Subclávio/diagnóstico , Idoso , Angina Pectoris/terapia , Angioplastia com Balão , Reestenose Coronária/terapia , Diagnóstico Diferencial , Feminino , Humanos , Complicações Pós-Operatórias/terapia , Retratamento , Síndrome do Roubo Subclávio/terapiaRESUMO
OBJECTIVES: To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis. DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial. SETTING: Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden. PATIENTS: 42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo. INTERVENTIONS: Patients received either an intravenous loading dose of 3000 IU AT III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo. MEASUREMENTS AND RESULTS: All patients were evaluated for safety and for 30-day all-cause mortality. CONCLUSIONS: The administration of AT III was safe and well-tolerated. It was followed by a 39 % reduction in 30-day all-cause mortality (NS). The reduction in mortality was accompanied by a considerably shorter stay in the ICU. Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II, multiple organ failure, organ system failure), which was noticeable soon after initiation of treatment. Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period. A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend. The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III. Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis.
Assuntos
Antitrombina III/uso terapêutico , Sepse/tratamento farmacológico , APACHE , Idoso , Causas de Morte , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Prospectivos , Sepse/complicações , Sepse/microbiologia , Sepse/mortalidade , Análise de SobrevidaRESUMO
BACKGROUND: The course of an inflammatory process is based upon complex interactions between the vessel wall and the humoral or cellular compounds of the vascular content as a consequence of a defense reaction. There are no substantial differences between the pathophysiology of local or of whole body inflammation on the molecular and cellular level. Sepsis, which is clinically regarded as a systemic inflammatory process requires the broad therapeutical spectrum of nowaday intensive care medicine, but still has a high mortality. The pathophysiology and clinical examples for both systemic and local inflammatory reactions are presented in this paper. Thereby, similar interactions between the vascular endothelium, the mediator systems to which the hemostatic system has to be considered as a part of, and the microcirculation remain in the foreground at first. Based on that, the use of polyvalent protease inhibitors in the therapy of local or systemic inflammatory reactions of different origin will be discussed. The spotlight falls on physiological inhibitors of the hemostatic and complement system, antithrombin III and C1-esterase inhibitor, which may have a regulatory function within these systems because of their multiple targets. CONCLUSION: The possibility of an adjuvant therapy of local or generalized inflammatory processes with physiologic protease inhibitors seems to be very promising. Nevertheless, at yet the substantial mechanisms of action are not fully understood.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Inibidores de Proteases/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Antitrombina III/administração & dosagem , Antitrombina III/efeitos adversos , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Inativadoras do Complemento 1/efeitos adversos , Endotélio Vascular/fisiopatologia , Hemostasia/fisiologia , Humanos , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Inibidores de Proteases/efeitos adversos , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologiaRESUMO
BACKGROUND: In contrast to persons with normal renal function, coronary risk factors or indicators until yet could not clearly be defined in renal insufficiency. PATIENTS AND METHODS: 30 patients under chronic hemodialysis therapy were investigated; 15 patients with severe coronary artery disease and 15 patients with normal coronary angiogram were compared. Numerous factors of the manner of living (diet, smoking behaviour etc.) were registered and glucose and lipid metabolism, hemostatic and fibrinolytic system as well as blood pressure level were investigated. RESULTS: Besides higher HDL-cholesterol and tissue plasminogen activator (TPA) levels in patients without coronary heart disease, no significant difference could be found between both groups. The higher HDL levels were mainly due to the higher percentage of women in the coronary healthy group. There was no evidence of insulin resistance as a major pathogenic factor in the group with coronary heart disease. The blood pressure levels were not significantly different in both groups. CONCLUSION: Our quantitative examination of accepted or suspected coronary risk factors revealed no entity which turned out to be a reliable risk indicator for practical purposes.
Assuntos
Glicemia/metabolismo , Pressão Sanguínea , Doença das Coronárias/sangue , Falência Renal Crônica/sangue , Estilo de Vida , Lipídeos/sangue , Diálise Renal , Idoso , Fatores de Coagulação Sanguínea/metabolismo , Pressão Sanguínea/fisiologia , Angiografia Coronária , Doença das Coronárias/diagnóstico , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinically defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient's status. The following measurements were undertaken: Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ failure (MOF) score, plasma levels of thrombin-antithrombin III complexes (TAT), antithrombin III (AT III), protein C antigen, factor XII, and plasminogen activator inhibitor type 1 antigen (PAI-1), neopterin, and interleukin 6 (IL-6). DESIGN: A prospective case series study. SETTING: Intensive care unit (ICU) of the Department of Internal Medicine, Justus Liebig University, Giessen, Germany. PATIENTS: 28 consecutive patients (11 females, 17 males; mean age 58 years) with clinically defined sepsis. Eleven patients were admitted from the surgical ICU (9 after elective surgery, 2 after trauma surgery). The operations were done 1-26 days (mean 14 days) prior to the onset of sepsis. MAIN RESULTS: At the onset of sepsis we found elevated plasma levels of TAT, PAI-1, neopterin, and IL-6, and lowered plasma levels of AT III, factor XII, and protein Cantigen. Neopterin, PAI-1, IL-6, and factor XII showed a statistically significant correlation with the APACHE II score. The MOF score is significantly correlated with IL-6 and neopterin. The extent of hemostatic abnormalities was related to increasing levels of IL-6. CONCLUSIONS: Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system, the vascular endothelium, and the monocyte/macrophage system. IL-6 may have a regulatory function for hemostasis in inflammation. Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis.
Assuntos
Endotélio Vascular/imunologia , Hemostasia/imunologia , Complicações Pós-Operatórias/imunologia , Sepse/imunologia , Índice de Gravidade de Doença , Adulto , Idoso , Antitrombina III/metabolismo , Biopterinas/análogos & derivados , Biopterinas/sangue , Estudos de Casos e Controles , Feminino , Humanos , Inflamação , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Neopterina , Inibidor 1 de Ativador de Plasminogênio/sangue , Complicações Pós-Operatórias/metabolismo , Estudos Prospectivos , Proteína C/metabolismo , Sepse/metabolismoRESUMO
In 19 patients on a low-dose aspirin therapy with 100 mg/d, an insufficient effect of aspirin was observed in five patients (aggregations induced by arachidonic acid and collagen, thromboxane B2-formation in serum and after collagen). Aspirin added in vitro increased the inhibition to a degree comparable to that seen in the other 14 patients, i.e. the insufficient effect could be due to a lack of compliance or to a reduced availability of the drug. In another 20 patients there was a good inhibitory effect of aspirin; additional aspirin did not increase the inhibition of arachidonic acid-induced aggregation and serum-thromboxane B2, but slightly increased collagen-induced aggregation and thromboxane B2 formation. The effect was the same, whether the aspirin was given in vivo or added in vitro.
Assuntos
Aspirina/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Araquidônico/farmacologia , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Colágeno/farmacologia , Doença das Coronárias/sangue , Doença das Coronárias/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Tromboxano B2/biossínteseAssuntos
Adenilil Ciclases/sangue , Alprostadil/farmacologia , Plaquetas/enzimologia , Epinefrina/farmacologia , Falência Renal Crônica/sangue , Uremia/sangue , Adulto , Colforsina/farmacologia , Humanos , Falência Renal Crônica/enzimologia , Falência Renal Crônica/terapia , Pessoa de Meia-Idade , Valores de Referência , Diálise Renal , Uremia/enzimologia , Uremia/terapiaRESUMO
Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor (PAI), D-dimer, euglobulin-clot-lysis-time (ECLT), plasminogen, alpha 2-antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II-score). An increase in D-dimer and t-PA-antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t-PA-activity was not detectable, PAI-function was elevated, the ECLT was prolonged and alpha 2-antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t-PA-antigen, PAI-function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II-score of the patients. We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, alpha 2-antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.
Assuntos
Infecções Bacterianas/sangue , Fibrinólise/fisiologia , Adulto , Idoso , Coagulação Sanguínea/fisiologia , Cuidados Críticos , Fator XII/análise , Feminino , Fibrinolisina/análise , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Plasminogênio/análise , Inativadores de Plasminogênio/sangue , Índice de Gravidade de Doença , Ativador de Plasminogênio Tecidual/sangue , alfa 2-Antiplasmina/análise , alfa-Macroglobulinas/análiseRESUMO
30 rabbits received an infusion of lipopolysaccharide B (75 micrograms/kg.h) over 4 hours (groups E, EI, EA; n = 10 each). Saline was given to a control group (C; n = 8). In group EI, prostacyclin (PGI2; 500 ng/kg.min) was given simultaneously to endotoxin. Into group EA animals, aspirin (20 mg/kg) was injected before the endotoxin infusion was started. PGI2 and aspirin both improved survival of animals (6/10 each vs. 2/10 in group E). The drop of platelet counts was significantly reduced by PGI2, while leukocyte depletion was similar in all endotoxin groups. PGI2 preserved the functional capacity of platelets as indicated by collagen stimulated aggregation and thromboxane formation. PGI2 but not aspirin significantly reduced renal fibrin deposition.
Assuntos
Epoprostenol/uso terapêutico , Choque Séptico/tratamento farmacológico , Animais , Aspirina/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Fibrina/metabolismo , Fibrinogênio/metabolismo , Lactatos/sangue , Ácido Láctico , Contagem de Leucócitos , Oxigênio/sangue , Tempo de Tromboplastina Parcial , Agregação Plaquetária , Contagem de Plaquetas , Tempo de Protrombina , Coelhos , Análise de Sobrevida , Tromboxano B2/sangueAssuntos
Fibrinólise , Sepse/sangue , Antitrombina III/metabolismo , Fator XII/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/sangue , Fibrinogênio/metabolismo , Glicoproteínas/sangue , Humanos , Plasminogênio/metabolismo , Inativadores de Plasminogênio , Contagem de Plaquetas , Tempo de Protrombina , Soroglobulinas/metabolismo , Ativador de Plasminogênio Tecidual/sangueAssuntos
Endotélio Vascular/metabolismo , Epoprostenol/biossíntese , Neutrófilos/metabolismo , 6-Cetoprostaglandina F1 alfa/biossíntese , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/metabolismo , Endotélio Vascular/efeitos dos fármacos , Técnicas In Vitro , Lipopolissacarídeos/farmacologia , Neutrófilos/efeitos dos fármacos , CoelhosRESUMO
Thirty rabbits received an infusion of lipopolysaccharide B (75 micrograms/kg.h) over 4 hours (groups E, EI, EA; n = 10 each). Saline was given to a control group (C; n = 8). In group EI, prostacyclin (PGI2; 500 ng/kg.min) was given simultaneously to endotoxin. Into group EA animals, aspirin (20 mg/kg) was injected before the endotoxin infusion was started. PGI2 and aspirin both improved survival of animals (6/10 each vs. 2/10 in group E). The drop of platelet counts was significantly reduced by PGI2, while leukocyte depletion was similar in all endotoxin groups. PGI2 preserved the functional capacity of platelets as indicated by collagen stimulated aggregation and thromboxane formation. PGI2 but not aspirin significantly reduced renal fibrin deposition.
Assuntos
Epoprostenol/farmacologia , Choque Séptico/prevenção & controle , Animais , Aspirina/farmacologia , Células Sanguíneas/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Feminino , Lipopolissacarídeos , Masculino , Coelhos , Choque Séptico/sangue , Choque Séptico/induzido quimicamenteRESUMO
In a trauma model of atherosclerosis (repeated mechanical injury of the rabbit ear artery), rabbits were pretreated either with etoposid (inducing a monocytopenia) or with prednisolone (inhibiting monocyte function) to investigate the role of monocytes in traumatically induced plaque formation. Three weeks after the last injury the arteries were carefully examined. While a profound monocytopenia during the period of injuries did not at all influence the size of the plaque formation, this was almost completely inhibited in the prednisolone-treated rabbits. Obviously, the effect of prednisolone must be attributed to other pharmacological properties. Monocytes appear to be of less importance in purely trauma atherosclerosis models.
Assuntos
Artérias/patologia , Arteriosclerose/sangue , Monócitos/fisiologia , Animais , Arteriosclerose/patologia , Modelos Animais de Doenças , Etoposídeo/farmacologia , Feminino , Hematócrito , Contagem de Leucócitos , Leucopenia/patologia , Prednisolona/farmacologia , CoelhosRESUMO
Human fibrinogen is phosphorylated in vivo to an equal extent at two positions, one at Ser 3 located on fibrinopeptide A, the other at Ser 345 of the A alpha-chain. As has been shown previously, the degree of phosphorylation of the circulating fibrinogen pool can be determined in vitro from the ratio between the HPLC peaks formed by phosphorylated and non-phosphorylated fibrinopeptide A which has been cleaved from plasma fibrinogen by thrombin or reptilase. Plasma samples were obtained from patients with venous thrombosis undergoing fibrinolytic therapy with urokinase (n = 8). The degree of phosphorylation increased from about 35% before treatment to values between 50% and 70% within 48 hours. It remained at these high levels as long as urokinase was administered and declined slowly thereafter. This behaviour of the degree of phosphorylation of fibrinogen is explained by a model which assumes that fibrinogen is secreted in the phosphorylated form and then dephosphorylated in the circulation by an up to now unidentified phosphatase by first order kinetics. When this system is in steady state, the degree of phosphorylation is about 25% under normal conditions. If the elimination rate of fibrinogen is greatly enhanced by fibrinogenolysis the system will approach a new steady state with a higher degree of phosphorylation, the magnitude of which will depend on the new ratio of dephosphorylation and elimination.
Assuntos
Fibrinogênio/metabolismo , Fibrinolíticos/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Circulação Sanguínea , Cromatografia Líquida de Alta Pressão , Feminino , Fibrinogênio/análise , Fibrinolíticos/farmacologia , Fibrinopeptídeo A/análise , Fibrinopeptídeo A/metabolismo , Humanos , Masculino , Fosforilação , Conformação Proteica , Tromboflebite/sangue , Tromboflebite/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/farmacologiaAssuntos
Epoprostenol/uso terapêutico , Choque Séptico/tratamento farmacológico , 6-Cetoprostaglandina F1 alfa/sangue , Animais , Fibrina/metabolismo , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Lipopolissacarídeos , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas/efeitos dos fármacos , Coelhos , Choque Séptico/sangue , Tromboxano B2/sangueRESUMO
Disorders of the coagulation system in shock are caused by injuries of the endothelium, influx of thromboplastic material into the blood and stasis. In this way, the intrinsic and the extrinsic system is activated. Fibrin is generated in the blood stream and forms high molecular complexes together with fibrinogen (hypercoagulability). With progress of the shock fibrin can deposit in the small vessels with the consequence of impaired circulation. Finally clotting factors and inhibitors (e.g. antithrombin III) are consumed by disseminated intravascular coagulation. This results in a bleeding tendency (consumption coagulopathy). In this survey particular shock formes (endotoxin induced, cardiogenic, traumatic, hemorrhagic) are discussed with regard to the reflections of the blood coagulation. The therapy of shock-induced disorders of blood coagulation are focused on treatment of primary disease, prevention or elimination of microthrombi, substitution of blood respective plasma components.
Assuntos
Coagulação Sanguínea , Choque/sangue , Fibrina/fisiologia , Hemostasia , Humanos , Inibidores de Proteases/sangue , Choque/terapiaRESUMO
The therapeutic regimen in acute pulmonary embolism of different severity is discussed. Heparin is indicated in patients with only small and submassive embolism without impairment of the circulation. Fibrinolysis is the therapy of choice in submassive pulmonary embolism with circulatory insufficiency and massive embolism. In fulminant embolism with circulatory shock or cardiac arrest embolectomy should be performed. If the course of lung embolism is subacute, fibrinolysis may improve the late prognosis in respect to chronic pulmonary hypertension.