RESUMO
Platelet thrombus formation on collagen fibrils is most pronounced at the upstream end of the surface, and it gradually decreases along the axis in parallel with the direction of the blood flow. This phenomenon, known as axial dependent platelet thrombus formation, is explained by the balance of the platelet supply to the surface and the consumption of platelets by growing thrombi. In the present study we have affected this balance by (A) inhibiting the growth of platelet thrombi by aspirin (ASA) or clopidogrel, and thus increasing the platelet concentration at the surface, and by (B) utilising blood from cigarette smokers, who have enhanced thrombus formation immediately after smoking, and thus decreasing the platelet concentration at the surface. Thrombus formation in non-anticoagulated blood was triggered by collagen fibrils positioned in a parallel-plate perfusion chamber at a wall shear rate of 2600 s-1 which is characteristic for moderately stenosed arteries. Morphometrical assessment of thrombus formation was performed at axial positions of 1 and 13 mm downstream to the blood flow inlet at the collagen surface. Platelet-collagen adhesion and thrombus volume in blood from nonsmokers were decreased at the downstream location by 39% (p < or = 0.0001) and by 60% (p < or = 0.0001), respectively. However, increasing the platelet concentration at the surface by partially inhibiting the thrombus growth by ASA or clopidogrel, reduced substantially the axial decrease in platelet adhesion and thrombus volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Colágeno/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Aspirina/farmacologia , Clopidogrel , Colágeno/metabolismo , Fibrina/metabolismo , Hemorreologia , Humanos , Masculino , Perfusão , Agregação Plaquetária/efeitos dos fármacos , Fumar/sangue , Estresse Mecânico , Propriedades de Superfície , Ticlopidina/análogos & derivados , Ticlopidina/farmacologiaRESUMO
Since the role of leukocytes found present in thrombi and haemostatic plugs is not clearly understood. we have investigated the interaction between leukocytes and growing thrombi in a human ex vivo model of arterial thrombogenesis. At a wall shear rate characteristic of moderately stenosed arteries (2600 s(-1)), granulocytes selectively accumulated at the luminal surface of platelet thrombi. The leukocyte adhesion seemed independent of fibrin formation and was clearly correlated to thrombus growth and platelet activation. In contrast, flow cytometry revealed that the expression of adhesion molecules (CD11a, CD11b, CD11, CD3, CD14, CD62L, HLA-DR and binding of fibrinogen) on the surface of circulating leukocytes passing the thrombi was, on short term conditions (15 min), independent of thrombus growth. The adhered granulocytes probably play a pivotal role in limiting the size of the evolving thrombi, as suggested by our electron micrographs of the arterial thrombi showing lysed and phagocytosed platelets. Thus, granulocytes might play an active role in the acute/semiacute phase of local thromboregulation.
Assuntos
Leucócitos/fisiologia , Trombose/patologia , Adulto , Coagulação Sanguínea , Plaquetas/fisiologia , Adesão Celular , Moléculas de Adesão Celular/análise , Colágeno/farmacologia , Antígenos HLA-DR/análise , Hemorreologia , Humanos , Imunofenotipagem , Masculino , Microscopia Eletrônica , Ativação Plaquetária , Adesividade PlaquetáriaRESUMO
In the present study we have investigated the effect of a 100 mg single oral dose of a newly developed thromboxane A2 receptor antagonist on collagen-induced thrombogenesis in flowing human non-anticoagulated blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils on a cover slip placed in a parallel-plate perfusion chamber. Shear rates at the collagen surface were characteristic for medium sized (650 s-1) and moderately stenosed (2,600 s-1) arteries. Blood-collagen interactions were morphologically quantified as platelet-collagen adhesion, fibrin deposition and thrombus volume. Activation peptides of coagulation, fibrinopeptide A (FPA), and of platelets, beta-thromboglobulin (beta-TG), were measured immediately distal to the perfusion chamber. HN-11500 ingestion reduced significantly the thrombus volume by 32% at 2,600 s-1, but not at 650 s-1. However, transmission electron microscopy revealed loosely packed and less degranulated platelets at 650 s-1. The beta-TG plasma levels were also reduced at both shear rates by the HN-11500 ingestion. The platelet-collagen adhesion was significantly enhanced at both shear rates. This was apparently a consequence of higher platelet concentrations at the collagen surface, because fewer platelets were consumed by the thrombi after the drug ingestion. In contrast, the coagulation, as measured by fibrin deposition and FPA plasma levels, was not significantly affected by HN-11500. Thus, it appears that the thromboxane A2 receptor antagonist HN-11500 reduces the thrombotic response by primarily impairing the platelet function at arterial blood flow conditions, and particularly at high wall shear rates.
Assuntos
Acetatos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/farmacologia , Hemodinâmica , Receptores de Tromboxanos/antagonistas & inibidores , Tiofenos/farmacologia , Administração Oral , Adulto , Colágeno/farmacologia , Fibrinopeptídeo A/análise , Humanos , Masculino , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Estresse Mecânico , beta-Tromboglobulina/análiseRESUMO
The goal of the present study was to investigate the effect of 7 and 14 days of daily oral administration of 75 mg clopidogrel on collagen-induced thrombogenesis in flowing non-anticoagulated human blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils positioned in a parallel-plate perfusion chamber. The wall shear rates at the collagen surface were those characteristic for veins (100 s-1), and for medium sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Clopidogrel ingestion reduced the thrombus volume significantly (p < 0.05) at 100 and 2600 s-1 (39 and 51% respectively). The beta-thromboglobulin plasma levels were reduced concomitantly. However, it was not possible to measure accurately the thrombus volume at 650 s-1, due to loose packing of the platelet thrombi. Transmission electron microscopy substantiated this observation and showed that clopidogrel profoundly reduced the platelet degranulation process (p < 0.005). The inhibitory effect of clopidogrel on platelet consumption by the growing thrombi resulted apparently in higher platelet concentration at the collagen surface, which enhanced the platelet-collagen adhesion at all three shear rates (p < 0.05). Despite the low deposition of fibrin on collagen, clopidogrel reduced significantly the fibrinopeptide A plasma levels and the fibrin deposition at shear rates below 650 s-1. This was apparently a consequence of the reduced platelet recruitment and the lower activation of platelets, since activated platelets in thrombi promote deposition of fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Inibidores da Agregação Plaquetária/farmacologia , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Adulto , Anticoagulantes , Velocidade do Fluxo Sanguíneo , Clopidogrel , Fibrina/metabolismo , Fibrinopeptídeo A/metabolismo , Testes Hematológicos , Humanos , Masculino , Ativação Plaquetária , Adesividade Plaquetária/efeitos dos fármacos , Contagem de Plaquetas/efeitos dos fármacos , Ticlopidina/farmacologiaRESUMO
The purpose of the present study was to investigate and to compare the interactions of platelets and proteins in flowing non-anticoagulated human blood with the biomaterials polyethylene-terephthalate (Dacron) and polytetrafluoroethylene (PTFE, Teflon). The respective biomaterials were positioned in a parallel-plate perfusion chamber, and exposed to flowing blood for 5 min at wall shear rates characteristic for veins (100/s), medium sized (650/s) and moderately stenosed arteries (2,600/s). Blood-material interactions were morphologically quantified as platelet-surface adhesion, thrombus volume and fibrin deposition. Platelet adhesion to Dacron was highest at the lowest shear rate (13%) and decreased with increasing shear (4% at 2600/s). In contrast, platelet adhesion to PTFE was shear rate independent (17-19%), and significantly higher than the adhesion to Dacron at 2600/s (P < 0.05). A hallmark of the platelets adherent to PTFE and Dacron was the large percentage of platelets not spread out on the surface. This indicates that both materials were poor platelet activators, even though immunostaining demonstrated the adsorption of the platelet adhesive proteins von Willebrand factor and fibronectin. Adsorption of fibrinogen was also prevailing on both materials. Virtually no thrombi formed on Dacron, while a few small platelet thrombi were observed on PTFE. Less than 1% of the Dacron and PTFE surfaces were covered by fibrin, irrespective of the shear rate. Thus, Dacron and PTFE interact differently with flowing non-anticoagulated human blood, and Dacron is apparently the least thrombogenic material.
Assuntos
Plaquetas/fisiologia , Proteínas Sanguíneas/metabolismo , Polietilenotereftalatos , Politetrafluoretileno , Adsorção , Adulto , Materiais Biocompatíveis , Fenômenos Biomecânicos , Colágeno/metabolismo , Feminino , Fibrina/metabolismo , Fibrinogênio/metabolismo , Fibronectinas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Varredura , Adesividade Plaquetária , Fator de von Willebrand/metabolismoRESUMO
We have studied the effect of a daily supplement of 2.4 omega-3 fatty acids (omega 3 FAs) to 16 healthy men on acute collagen-induced thrombus formation in flowing non-anticoagulated blood. The supplement was formulated as Triomar capsules, containing 60% omega-3 FAs with an eicosapentaenoic/docosahexaenoic acid ratio of 3/2. A parallel-plate perfusion chamber device was used to study thrombus formation prior to and after 3 months of omega-3 FAs supplement. The wall shear rates at the thrombogenic surface were 650, 2,600 and 10,500 s-1, which are typical for small arteries, slightly stenosed arteries and severely stenosed arteries, respectively. For the latter situation a parallel-plate perfusion chamber with an eccentric stenosis occluding 80% of the cross-sectional area of the blood flow channel was used. The dietary supplement of omega-3 FAs did not cause significant changes in platelet adhesion to collagen or in thrombus volume. However, fibrin deposition was reduced by 34% (P < 0.03) at the highest shear condition (stenosis). Plasma fibrinogen was reduced by 18% (P < 0.0006). Changes in serum concentration of triglycerides, total-cholesterol, LDL- and HDL-cholesterol were not significant. Our data suggest that a moderate intake of omega-3 FAs provides virtually no protection against acute platelet-dependent thrombus formation, irrespective of the shear conditions. However, the significant reduction in plasma levels of fibrinogen following dietary supplementation of omega-3 FAs may be important, since high levels of fibrinogen is associated with cardiovascular disease and thrombosis.
Assuntos
Colágeno , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Trombose/prevenção & controle , Adulto , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Gorduras Insaturadas na Dieta/uso terapêutico , Ácidos Graxos/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Fibrinopeptídeo A/análise , Humanos , Masculino , Fosfolipídeos/sangue , Trombose/induzido quimicamente , beta-Tromboglobulina/análiseRESUMO
Many women desire some kind of reconstruction after mastectomy for breast cancer to improve the cosmetic result. Since the introduction of silicone breast implants, capsular contracture has been the most common complication of breast augmentation or reconstruction. The aim of the present study was to evaluate the capsule quality in patients with breast cancer who had undergone reconstructions with either textured (rough) or smooth silicone implants after simple or modified radical mastectomy. Forty-three consecutive patients had reconstructions with textured silicone implants (49 implants) and were evaluated 32 months post-operatively in a prospective clinical trial. The last 43 consecutive patients who had reconstructions with bilumen smooth silicone implants (49 implants) acted as controls. The results were graded by Baker's classification. Among the patients with textured implants only 9% (4/47) was graded as having moderate or severe capsular contracture in contrast to 24% (11/46) in patients with bilumen smooth-surface implants (p < 0.05). These results confirm previous reports that favour textured silicone implants in breast augmentation and reconstruction.
Assuntos
Implantes de Mama , Mastectomia , Silicones , Feminino , Humanos , Mamoplastia , Mastectomia Radical , Mastectomia SimplesAssuntos
Meios de Contraste , Absorção Intestinal/efeitos dos fármacos , Obstrução Intestinal/diagnóstico por imagem , Intestinos/diagnóstico por imagem , Iohexol , Ácidos Tri-Iodobenzoicos , Cromatografia Líquida de Alta Pressão , Meios de Contraste/efeitos adversos , Meios de Contraste/análise , Método Duplo-Cego , Humanos , Obstrução Intestinal/urina , Iohexol/efeitos adversos , Iohexol/urina , Radiografia , Fatores de Tempo , Ácidos Tri-Iodobenzoicos/efeitos adversos , Ácidos Tri-Iodobenzoicos/urinaRESUMO
BACKGROUND: This study aims to investigate whether cosmetic surgery has an effect on an individual's body image, general self-esteem, and psychological problems. Further tests were conducted to assess whether the extent of psychological problems before surgery influenced improvements in postoperative psychological outcomes. METHODS: Questionnaire data from 155 female cosmetic surgery patients from a plastic surgery clinic were obtained before and approximately 6 months after surgery. The questionnaire consisted of measures on body image, self-esteem, and psychological problems. Pre- and postoperative values were compared. Pre- and postoperative measures were also compared with the data compiled from a representative sample of 838 Norwegian women, aged 22-55, with no cosmetic surgery experience. RESULTS: No differences in psychological problems between the presurgery patient and comparison samples were found, whereas differences in body image and self-esteem between the sample groups were reported in an earlier publication. Analyses further revealed an improvement in body image (satisfaction with own appearance) after surgery. A significant but rather small effect on self-esteem was also found, whereas the level of psychological problems did not change after surgery. Postoperative measures of appearance satisfaction, self-esteem, and psychological problems did not differ from values derived from the comparison sample. Finally, few psychological problems before surgery predicted a greater improvement in appearance satisfaction and self-esteem after surgery. CONCLUSIONS: The study provides evidence of improvement in satisfaction with own appearance after cosmetic surgery, a variable that is thought to play a central role in understanding the psychology of cosmetic surgery patients. The study also points to the factors that surgeons should be aware of, particularly the role of psychological problems, which could inhibit the positive effects of cosmetic surgery.
Assuntos
Imagem Corporal , Transtornos Mentais/psicologia , Procedimentos de Cirurgia Plástica/psicologia , Autoimagem , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários , Adulto JovemRESUMO
Between 1979 and 1989, 38 patients were treated for cancer of the oesophagus. 25% (21/38) of the patients underwent resection of the oesophagus with either curative or palliative measures. 12 patients were treated radically, of whom two (17%) have lived free of recurrence for more than five years. Radical thoracoabdominal oesophageal resection is recommended as long as the operative mortality is low. Careful preoperative evaluation is necessary to select patients who should be treated by palliative procedures, such as oesophageal resection, by-pass procedures, laser coagulation and/or local irradiation.
Assuntos
Neoplasias Esofágicas/cirurgia , Idoso , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Complicações Pós-Operatórias/mortalidade , PrognósticoRESUMO
204 male patients aged 16 years and older who had been operated for acquired inguinal hernia at Sarpsborg Sykehus during the period 1975-81 were reexamined by means of a personal follow-up examination. Before the operation the patients were randomized into two different groups. One group was operated using Bassini's technique and the other using Hindmarsh's technique. This prospective clinical study revealed far fewer recurrences after the Hindmarsh operation. The recurrence rate of all inguinal herniae treated by the Hindmarsh operation was 7.4%, as against 18.7% in cases treated by the Bassini operation. Our study shows that the operative procedure chosen for treatment of acquired inguinal hernia is a variable affecting the rate of recurrence.
Assuntos
Hérnia Inguinal/cirurgia , Adulto , Seguimentos , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Estudos Prospectivos , RecidivaRESUMO
Definite sonographic abnormalities are noted short time after the onset of acute testicular pain in patients with testicular torsion. In some cases gray-scale sonographic features will prove valuable in differentiating epididymo-orchitis from torsion. The spectrum of findings include testicular enlargement with an associated decrease in echogenicity of the testicular parenchyma, enlargement of the epididymal body and spermatic cord, and sometimes a hydrocele. A case is presented, in which the B-scan ultrasound mapped out the intrascrotal contents and caused prompt surgical intervention.
Assuntos
Torção do Cordão Espermático/diagnóstico , Ultrassonografia , Adolescente , Humanos , Masculino , Torção do Cordão Espermático/cirurgiaRESUMO
We studied the incidence of hip fractures in the county of Troms. This was compared with the incidence in a district of the city of Oslo. In both regions, the incidence increased almost exponentially with age both for men and for women. Since 1978, age-adjusted incidence has increased. This is most pronounced for men and for the county of Troms. In 1978 there was a marked difference between Oslo and Troms as regards risk of hip fracture. In 1989 this difference had diminished and persisted only among very old people. Risk factors other than postmenopausal and senile osteoporosis are discussed in an attempt to explain this development.
Assuntos
Fraturas do Quadril/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Fatores de RiscoRESUMO
We investigated the combined effect of wall shear rate and immobilized collagen on platelet activation in flowing nonanticoagulated human blood. By combining an ex vivo model of thrombogenesis with flow cytometry, we showed that activated platelets can be detected in the bloodstream passing growing thrombi at a wall shear rate characteristic of moderately stenosed arteries (2600 s-1). The activation of the circulating platelets was clearly correlated with thrombus growth. Different antibodies against platelet activation-dependent surface markers had distinct sensitivity to the thrombotic process. alpha-Granule release detected by surface expression of CD62P seemed to be the most sensitive marker, as judged by both mean fluorescence intensity and fraction of platelets activated. The conformational change in glycoprotein IIb-IIIa, as detected by PAC-1, also seemed to be a sensitive marker and preceded binding of fibrinogen to activated glycoprotein IIb-IIIa, as detected by anti-fibrinogen. Large thrombi also elicited lysosome exocytosis, detected by surface expression of CD63. Finally, we observed a small decrease of glycoprotein Ib-IX expression, as detected by anti-CD42a. Thus, our study provides further information on the dynamics of platelet activation in relation to thrombus growth at arterial shear conditions in flowing nonanticoagulated human blood.
Assuntos
Coagulação Sanguínea , Velocidade do Fluxo Sanguíneo , Ativação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/ultraestrutura , Trombose , Adulto , Antígenos CD/metabolismo , Plaquetas/metabolismo , Degranulação Celular , Exocitose , Fibrinogênio/metabolismo , Humanos , Técnicas Imunológicas , Lisossomos/fisiologia , Masculino , Modelos Biológicos , Selectina-P/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Reologia , Tetraspanina 30RESUMO
The relative importance of vessel wall tissue factor (TF) in initiating thrombogenesis is not well defined. In contrast, vessel wall collagens have been well documented as potent inducers of thrombus formation. We compared the potency of a human TF/phospholipid surface with that of a surface consisting of human type III collagen fibrils in triggering thrombus formation in native human blood at venous and arterial blood flow conditions. A commercial preparation, Thromborel S, was used as a source of human TF. Biochemical characterization of this preparation revealed small amounts of FVII, FIX, and FX proteins. Coagulant activity of these proteins was associated with the FVII protein only, although it was a very low activity. Studies with anti-TF antibodies in a one-stage clotting assay showed that the procoagulant activity of Thromborel was mainly a result of TF. The molar ratio of TF to phospholipid was 1:2 x 10(7). Thrombus formation in flowing nonanticoagulated human blood drawn directly from an antecubital vein was triggered by either Thromborel S or collagen fibrils coated on Thermanox coverslips in a parallel-plate perfusion chamber device. A 1:50 Thromborel S dilution gave maximal fibrin deposition (90% surface coverage) at a wall shear rate of 100 s-1. However, pretreatment of the TF surface with a monoclonal anti-TF antibody reduced this fibrin deposition by 93% (P < .001). Thus, TF was essential for the procoagulant activity of the Thromborel S surface in this flow system also. At higher wall shear rates (650 and 2600s-1), less fibrin was deposited, but the platelet thrombus formation on the fibrin mesh increased dramatically.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Coagulação Sanguínea , Colágeno/fisiologia , Tromboplastina/fisiologia , Trombose/sangue , Fatores de Coagulação Sanguínea/análise , Fatores de Coagulação Sanguínea/fisiologia , Velocidade do Fluxo Sanguíneo , Plaquetas/ultraestrutura , Fibrina/ultraestrutura , Humanos , Fosfolipídeos/sangue , Tromboplastina/análise , Trombose/fisiopatologiaRESUMO
The precipitating event leading to stroke, myocardial infarction, and/or sudden death may be related to the formation of mural thrombus at the site of a ruptured or superficially damaged stenotic plaque. The fluid dynamic properties at atherosclerotic plaques that may be implicated in this thrombus formation have been described in a wide variety of model systems in both the process of plaque rupture and the growth of platelet thrombi. In general, the local fluid dynamic conditions are complex and show major variations from flow in well-defined laminar flow systems. However, no studies have attempted to quantify the effect of stenosis-related disturbances on thrombus formation in native human blood and to compare them with the local fluid dynamics. We developed a parallel-plate perfusion chamber device in which thrombus formation is measured at the "apex" of eccentric stenoses and have correlated such measurements with values of the local fluid dynamics obtained by computer simulation. The extent of stenoses (reduction in the cross-sectional area of the blood flow channel) was 60%, 80%, and 89%, corresponding to "apex" wall shear rates of 2600, 10,500, and 32,000 sec-1, respectively. The wall shear rate in the laminar flow region proximal and distal to the stenoses was 420 sec-1. The surface of the stenosis was purified collagen type III fibrils that were exposed to flowing nonanticoagulated human blood drawn directly from an antecubital vein by a pump placed distally to the perfusion chamber. The resulting blood-collagen interactions were quantified by light microscopy by using a morphometric image analysis technique. Under all conditions studied, platelet thrombus formation at the "apex" was extensive.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Arteriosclerose/fisiopatologia , Hemorreologia , Modelos Cardiovasculares , Trombose/fisiopatologia , Arteriosclerose/sangue , Arteriosclerose/patologia , Velocidade do Fluxo Sanguíneo , Colágeno/fisiologia , Humanos , Adesividade Plaquetária , Trombose/sangue , Trombose/patologiaRESUMO
The authors discuss the dilemmas associated with diagnosis and treatment of haemangiomas and vascular malformations. The complexity of these conditions too often sends the patients wandering from one specialist to another in search of an optimal therapeutic approach. We have established a multidisciplinary team to facilitate interspecialty communication on diagnosis, natural history, and therapy.
Assuntos
Malformações Arteriovenosas , Hemangioma , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/terapia , Hemangioma/diagnóstico , Hemangioma/patologia , Hemangioma/terapia , HumanosRESUMO
To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear.
RESUMO
Cigarette smoking is a known risk factor for cardiovascular disease in men and women, and it has been suggested that this risk is linked to enhanced formation of platelet thromboxane A2 (TxA2). This led us to investigate the effect of cigarette smoking and TxA2 formation on collagen-induced thrombogenesis in flowing nonanticoagulated human blood. Thrombus formation in blood from smokers and nonsmokers was compared before and 2 hours after ingestion of a single oral dose of 990 mg aspirin, which is sufficient to block platelet TxA2 formation. Nonanticogulated blood was drawn directly from an antecubital vein over collagen fibrils in a parallel-plate perfusion chamber by a peristaltic roller pump placed distally to the chamber. Wall shear rates at the collagen surface were characteristic for medium-sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Blood-collagen interactions were morphologically quantified, and markers of platelet release, beta-thromboglobulin (beta-TG), and activation of coagulation, fibrinopeptide A (FPA), were measured immediately distal to the perfusion chamber. The thrombus volume in blood from cigarette-smoking individuals was nearly twofold larger than in blood from nonsmokers at 2600 s-1 (37.4 and 19.4 microns 3/microns 2; P < .03). However, ingestion of aspirin reduced the thrombus volume in blood from smokers by 61.8% (P < .01), which was substantially more than the 37.6% reduction in blood from nonsmokers (P < .03). Neither cigarette smoking nor aspirin ingestion affected thrombus formation at 650 s-1. The plasma levels of FPA and beta-TG were slightly lower in nonsmokers and after aspirin ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Artérias/patologia , Aspirina/farmacologia , Fumar , Trombose/prevenção & controle , Adulto , Artérias/metabolismo , Plaquetas/fisiologia , Adesão Celular/efeitos dos fármacos , Colágeno , Constrição Patológica/metabolismo , Constrição Patológica/patologia , Feminino , Fibrina/metabolismo , Fibrinopeptídeo A/metabolismo , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Trombose/fisiopatologia , beta-Tromboglobulina/metabolismoRESUMO
The objective of the present study was to investigate collagen-induced platelet thrombus formation at arterial blood flow conditions in nonanticoagulated blood from habitual smokers and from nonsmoking patients with severe peripheral atherosclerotic disease. Collagen-induced thrombogenesis was elicited in native blood drawn directly from an antecubital vein over immobilized type III collagen fibrils coated on a coverslip positioned in a parallel-plate perfusion chamber. The wall shear rates at the collagen surface were comparable to those encountered in medium-sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Thrombus formation in blood from habitual smokers after 10 hours of smoking abstinence appeared to be not different from thrombus formation in blood from healthy nonsmokers. However, immediately after a cigarette had been smoked, thrombus volume in blood from the same individuals was increased twofold at the highest shear rate (P < .05). Thus, the thrombotic response was temporarily upregulated after smoking. Thrombus formation in blood from nonsmoking patients with severe peripheral atherosclerotic disease was neither enhanced nor decreased but was within the range of the nonsmoking control subjects. However, fibrinopeptide A generation after 4 minutes of perfusion at 2600 s-1 was higher in blood from the atherosclerotic patients (P < .05) and associated with a higher plasma fibrinogen level (P < .005). Thus, signs of changed platelet reactivity in flowing nonanticoagulated blood were encountered only in the habitual smokers immediately after they had smoked a cigarette.