RESUMEN
Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.
Asunto(s)
Iloprost/uso terapéutico , Interleucina-6/metabolismo , Isquemia/tratamiento farmacológico , Extremidad Inferior/irrigación sanguínea , Receptores Tipo II del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Isquemia/metabolismo , Masculino , Monocitos/efectos de los fármacos , Monocitos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/antagonistas & inhibidores , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
AIM: Iloprost, usually administered through intravenous infusion for 6 hours per day for at least 21 days, is the main medical treatment for critical limb ischemia in patients unsuitable for surgical or endovascular approach. We evaluated the tolerance and the short-term and long-term effects of a single 1-week treatment in critical limb ischemia patients. METHODS: Twenty-nine patients in Leriche-Fontaine III and IV stage were treated with iloprost infusions for 16 hours per day for 7 days, achieving a maximal dose of 1.5 ng/kg/min. Tolerance and clinical assessment after treatment discontinuation and after 1 and 6 months were recorded; clinical evaluation (rest pain, trophic lesions), ankle/brachial pressure index (ABPI) and treadmill exercise test were performed before, immediately after treatment and after 1 and 6 months. RESULTS: No discontinuation of treatment occurred because of intolerance to iloprost. At the end of the treatment 69% of patients were responders, 55.2% at 1 month, 37.9% after 6 months. ABPI and treadmill maximum walking distance were improved by the treatment at every timepoint. After 6 months 10.3% mortality and 3.4% major amputation rates were recorded. There was a higher percentage of non-responders amongst women vs men, in diabetic patients vs non diabetic and in stage IV patients vs stage III. CONCLUSIONS: One-week treatment with iloprost is safe and effective in both Leriche-Fontaine stage III and IV patients. Clinical effects are persistent over time, often lasting up to the 6th month, similarly to the commonly used 28-day treatment, with clear implications in terms of patient's compliance and medical cost containment.
Asunto(s)
Iloprost/administración & dosificación , Vasodilatadores/administración & dosificación , Anciano , Anciano de 80 o más Años , Prueba de Esfuerzo , Femenino , Humanos , Infusiones Intravenosas , Isquemia , Masculino , Persona de Mediana EdadRESUMEN
The authors report a randomised double-blind clinical study on the efficacy and tolerability of flunarizine. Two groups of patients with obliterating peripheral arterial disease (stage II) were treated for 3 months either with 10 mg flunarizine or with placebo and were examined monthly as to subjective symptoms, laboratory and instrumental parameters. Findings were evaluated by analysis of variance and Student's t-test. After three months, the flunarizine group had a greater increase of the distance walked before the onset of claudication and of maximum post-ischemic blood flow. No changes were observed in laboratory tests and central hemodynamics. The score of subjective symptoms was improved in the flunarizine treated group. Tolerance was good, side effects requiring withdrawal of treatment were not observed.
Asunto(s)
Arteriosclerosis Obliterante/tratamiento farmacológico , Flunarizina/uso terapéutico , Claudicación Intermitente/tratamiento farmacológico , Anciano , Arteriosclerosis Obliterante/complicaciones , Arteriosclerosis Obliterante/fisiopatología , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Humanos , Claudicación Intermitente/fisiopatología , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Flujo Sanguíneo RegionalRESUMEN
The authors report the results of a double-blind cross-over study on calcium dobesilate in which two groups of eight recent-onset type-II diabetics were treated either p.o. (1 g once daily) or i.v. (500 mg in 100 ml of physiological saline) with calcium dobesilate or with placebo. During oral administration of the drug, blood rheology and total fibrinolytic capacity were assessed by calculating euglobulin lysis time. In view of the evidence for a viscosity-lowering action of the drug (which had already been found in "long-term" studies) and of potentiation of fibrinolytic activity, intravenous treatment was started with the object of elucidating the possible mechanisms of action, evaluating at the same time other parameters concerning the functional fibrinolytic pathways. It has thus been possible to ascertain that the drug has "rheologic" activity, interferes with the function of endothelial cells by stimulating the release of tissue plasminogen activator and thus increases fibrinolytic activity while not interfering with the clotting function and not altering platelet beta-thromboglobulin secretion. These findings appear to confirm the possibilities for therapeutic use of calcium dobesilate which is thought to act on a variety of pathogenetic mechanisms involved in diabetic microangiopathy.
Asunto(s)
Bencenosulfonatos/uso terapéutico , Viscosidad Sanguínea/efectos de los fármacos , Dobesilato de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Administración Oral , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Dobesilato de Calcio/administración & dosificación , Dobesilato de Calcio/farmacología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana EdadRESUMEN
A case of multicentric angiofollicular hyperplasia (hyaline-vascular type) associated with Kaposi sarcoma of lymph nodes is reported. The patient was a 75-year-old man who suffered from edema, fever, maculopapular skin rashes and polyclonal hypergammaglo-bulinemia and died 10 days after admission to hospital for acute tubular necrosis and pulmonary edema. No other localizations of Kaposi's sarcoma were detected at autopsy; this is a very uncommon finding in Western countries and in adult people.
Asunto(s)
Enfermedad de Castleman/complicaciones , Sarcoma de Kaposi/complicaciones , Anciano , Enfermedad de Castleman/patología , Humanos , Ganglios Linfáticos/patología , Masculino , Insuficiencia Multiorgánica/etiología , Edema Pulmonar/complicaciones , Sarcoma de Kaposi/patologíaRESUMEN
Pre-treatment with allopurinol is able markedly to attenuate the deterioration in blood viscosity (BV) and whole blood filterability (WBF) that occurs after ischaemia during exercise. It also reduces the exercise-induced increase in serum oxidase activity, although this action is slightly less effective in peripheral obliterative arterial disease (POAD) patients. Conversely, allopurinol is completely ineffective in modifying haemorheological parameters in vitro, and it does not affect superoxide anion generation or enzyme release from neutrophils stimulated in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP). It is suggested that allopurinol may attenuate changes in BV and WBF by affecting xanthine-oxidase-dependent free radical formation in tissues.
Asunto(s)
Alopurinol/farmacología , Viscosidad Sanguínea/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Anciano , Arteriopatías Oclusivas/sangre , Arteriopatías Oclusivas/tratamiento farmacológico , Enfermedad Coronaria/sangre , Femenino , Glucuronidasa/sangre , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Esfuerzo Físico , Reología , Superóxidos/sangreAsunto(s)
Viscosidad Sanguínea/efectos de los fármacos , Diatrizoato/farmacología , Deformación Eritrocítica/efectos de los fármacos , Yopamidol/farmacología , Adulto , Anciano , Método Doble Ciego , Femenino , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Distribución Aleatoria , ReologíaRESUMEN
Despite the methodological difficulties of evaluating the role of a single rheological component, some clinical situations characterised by an increase of blood viscosity can be identified. These are classified as 'blood hyperviscosity syndromes' and can be divided into 2 groups. The first includes pathophysiological conditions in which a primary blood abnormality causes a decrease of blood flow, as occurs in polycythaemic, sclerocythaemic and seric hyperviscosity syndromes, and may be referred to as 'primary blood hyperviscosity syndromes'. The second group includes pathological conditions in which a primary reduction of blood supply to tissue provokes tissue ischaemia, and an impairment of rheological properties of blood can be observed at microcirculatory level. Thus, these situations have been described as 'secondary blood hyperviscosity syndromes'. Patients with peripheral obliterative arterial disease, ischaemic cardiopathies and cerebrovascular insufficiencies show a diminution in blood fluidity during spontaneous or provoked ischaemic conditions which disappears after reperfusion of the tissue. The pathogenesis of this rheological damage is unclear, but may arise from the complex relationship among blood cells (red cells, leucocytes, platelets), endothelium and plasma components. In addition to these 2 groups of blood hyperviscosity syndromes, several pathological states such as diabetes, shock, surgery, and rheumatic disease have been described in which an increase of blood viscosity can be observed. For these situations, which require much further investigation, the term 'syndromes associated with blood hyperviscosity' could be proposed.
Asunto(s)
Viscosidad Sanguínea , Enfermedades Hematológicas/sangre , Enfermedades Hematológicas/etiología , Humanos , SíndromeRESUMEN
The hemorheologic changes in three groups of patients suffering from acute and chronic cerebrovascular diseases were studied. Firstly, a horizontal study on 57 patients with definite stroke and on 49 patients with TIA was made. Plasma viscosity, whole blood filtration rate, fibrinogen concentration and hematocrit were evaluated as markers of the rheological property of blood. Blood samples were drawn within 6 h from the onset of vascular syndrome. The findings were compared with values obtained in 112 as controls. At the same time, washed red cell filtration rate, together with lactoferrin, betaglucuronidase and beta-thromboglobulin plasma level were assayed. In both groups the onset of the vascular storm was associated with a marked increase of plasma fibrinogen and of blood and plasma viscosity and a significant decrease of whole blood filterability. Lactoferrin, betaglucuronidase and beta-thromboglobulin levels were also significantly increased. Following this, a longitudinal study was performed on 27 patients with definite stroke and 32 patients with TIA. The clinical regression of acute stroke was associated with the progressive reduction of rheological abnormalities. Finally, 81 patients with clinical diagnosis of cerebrovascular disease due to previous stroke or repeated TIA were studied together. An increase of blood viscosity, of fibrinogen concentration and of hematocrit and a decrease of blood filtration rate together with higher levels of beta-thromboglobulin were registered. These results confirm the existence of an association between CVD and hemorheological alterations and suggest more in depth research directed towards identifying the significance of these alterations in the pathogenesis of tissue ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Viscosidad Sanguínea , Trastornos Cerebrovasculares/sangre , Deformación Eritrocítica , Enfermedad Aguda , Adulto , Anciano , Enfermedad Crónica , Femenino , Hematócrito , Humanos , Ataque Isquémico Transitorio/sangre , Lactoferrina/sangre , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Reología , beta-Tromboglobulina/análisisRESUMEN
The authors show a new method to study erythrocyte aggregation; the results of in vitro study, obtained by modification of several parameters (hematocrit, immunoglobulins, fibrinogen concentrations), are exposed. The authors did not find in vivo correlations between MAE and hemorheological parameters in different diseases; they found low MAE values only in myelomatous subjects. Adding erythrocytes from healthy donors to myelomatous plasma and vice versa, they found low MAE values only in samples containing erythrocytes and plasma from myeloma. These results suggest that many factors, not only erythrocyte aggregability, contribute to determine MAE (Mean Aggregation Entity).
Asunto(s)
Agregación Eritrocitaria , Humanos , Luz , Métodos , Mieloma Múltiple/sangre , Reología , Dispersión de Radiación , Macroglobulinemia de Waldenström/sangreRESUMEN
It is well established that cerebral blood flow (CBF) is low in patients with high hematocrit and is high in anemic patients. An inverse relationship between CBF and hematocrit has been found. Furthermore, if hematocrit is reduced, CBF increases. There is some debate as to whether these observations are due to viscosity or to oxygen carrying capacity of the blood. In order to further elucidate this problem, CBF, blood viscosity and hematocrit were measured in 4 patients with paraproteinemias before and after paraproteins had been removed by plasmapheresis without changes in hematocrit. After plasmapheresis, blood viscosity significantly decreases and CBF increases by a mean of 24.4 ml/100 g/min. Mean arterial blood pressure and hematocrit were not influenced by plasmapheresis. These results indicate that blood viscosity is an important factor in determining CBF. This does not exclude the role of oxygen transport as an associated factor, but it is evident that oxygen transport and blood viscosity are independent variables in the control of CBF.
Asunto(s)
Viscosidad Sanguínea , Circulación Cerebrovascular , Hematócrito , Humanos , Mieloma Múltiple/fisiopatología , Oxígeno/sangre , Plasmaféresis , Flujo Sanguíneo RegionalRESUMEN
A new method to measure erythrocyte ATP levels is used. The authors have incubated 6 whole blood samples and 7 samples containing washed red blood cells for 6 h. They measured ATP levels and confirmed an important decrease of the values during the time. If the same samples were incubated with pentoxifylline (1.4 X 10(-4) M), the ATP decrease was less relevant.
Asunto(s)
Adenosina Trifosfato/sangre , Eritrocitos/metabolismo , Pentoxifilina/farmacología , Teobromina/análogos & derivados , Metabolismo Energético , Eritrocitos/efectos de los fármacos , Humanos , Mediciones Luminiscentes , MétodosAsunto(s)
Arteriopatías Oclusivas/sangre , Viscosidad Sanguínea/efectos de los fármacos , Colina/análogos & derivados , Citidina Difosfato Colina/farmacología , Enfermedades Hematológicas/inducido químicamente , Anciano , Eritrocitos/fisiología , Humanos , Masculino , Persona de Mediana Edad , Reología , SíndromeAsunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Pirrolidinas/uso terapéutico , Vasodilatadores/uso terapéutico , Administración Oral , Arteriopatías Oclusivas/sangre , Viscosidad Sanguínea , Femenino , Humanos , Concentración de Iones de Hidrógeno , Claudicación Intermitente/sangre , Claudicación Intermitente/tratamiento farmacológico , Lactatos/sangre , Ácido Láctico , Masculino , Persona de Mediana Edad , Esfuerzo Físico , Pirrolidinas/administración & dosificación , Vasodilatadores/administración & dosificaciónRESUMEN
A clinical study on the effects of the normovolemic hemodilution on hemorheological and peripheral hemodynamic parameters has been carried out in patients with peripheral obliterative arterial disease. Two sessions have been performed: the acute test consisted in daily normovolemic hemodilutions for a period of 7 days in 10 patients with the determination of hemorheological and peripheral hemodynamic parameters before and after each treatment. A chronic study was then carried out in 8 patients by applying weekly normovolemic hemodilutions, by evaluating the hemorheological parameters as in the first session and by measuring the peripheral hemodynamic parameters at the beginning, after 5 weeks and at the end of the treatment. The results are reported and the possible mechanism of action of normovolemic hemodilution is discussed.
Asunto(s)
Arteriopatías Oclusivas/terapia , Extremidades/irrigación sanguínea , Hemodilución , Viscosidad Sanguínea , Eritrocitos/fisiología , Femenino , Hematócrito , Humanos , Masculino , UltrafiltraciónRESUMEN
The aim of this study was to evaluate the possible action in vitro of the platelets on the rheological behavior of red blood cells in healthy subjects and in patients with peripheral obliterative arterial disease before and after an isotonic exercise. Red blood cells and platelets from control subjects and from patients were tested in several ratios before and after the exercise studying the erythrocyte filterability. beta-thromboglobulin, a platelet-specific protein, was determined in vivo in all subjects before and after the exercise and in vitro as percent of increase between PPP and PRP activated, to monitor the platelet release. The results showed the interrelationship between platelet activation and rheological behavior of red blood cells.
Asunto(s)
Arteriopatías Oclusivas/sangre , Eritrocitos/fisiología , Esfuerzo Físico , Agregación Plaquetaria , Ultrafiltración , Adulto , Anciano , Femenino , Humanos , Claudicación Intermitente/sangre , Masculino , Persona de Mediana Edad , Reología , beta-Tromboglobulina/análisisRESUMEN
This study has been performed to evaluate the in vivo effect of acetylsalicylic acid (ASA) i.v. infusion at two different dosages: 500 and 2,000 mg on the main hemorheological parameters (blood viscosity and filtrability, hematocrit) and on beta-thromboglobulin (a platelet-specific protein) in patients with peripheral obliterative arterial disease, before and after an ischemic exercise. The results obtained before and 3 and 24 h after the drug administration induced us to think that platelet-specific substances released during the ischemic exercise can affect the hemorheological parameters and that ASA may be able to interfere with these reactions by inhibiting the platelet release.