endothelin-1 and Thrombosis

One of the risk factors for developing cardiovascular disease (CVD) is aging. In the elderly endothelial dysfunction occurs as altered endothelial ability to regulate hemostasis, vascular tone and cell permeability. In addition, there are changes in the expression and plasma levels of important endothelial components related to endothelial-mediated modulation in hemostasis. These include alterations in the metabolism of nitric oxide and prostanoides, endothelin-1, thrombomodulin and Von Willebrand factor. These alterations potentiate the pro-coagulant status developed with aging, highlighting the endothelial role in the development of thrombosis in aging.

Topics: Aging; Animals; Disease Susceptibility; Endothelin-1; Endothelium, Vascular; Hemostasis; Humans; Nitric Oxide; Thrombomodulin; Thrombosis; von Willebrand Factor

Pulmonary arterial hypertension (PAH) refers to a group of diseases characterized by high pulmonary artery pressure of unknown mechanism. Primary pulmonary hypertension (PPH) is the idiopathic subset of PAH that affects a mostly young population and is more common in females than in males. A familial form of PPH accounts for about 6% of cases, and its autosomal dominant gene was recently identified. Pulmonary arterial hypertension is histologically characterized by endothelial and smooth muscle cell proliferation, medial hypertrophy, and thrombosis in situ. The pathogenesis of PAH remains unclear. Elevated pulmonary vascular resistance seems to result from an imbalance between locally produced vasodilators and vasoconstrictors, in addition to vascular wall remodeling. Nitric oxide, a locally produced selective pulmonary vasodilator, appears to play a central role in the pathobiology of PAH.

Topics: Endothelial Growth Factors; Endothelin-1; Endothelium, Vascular; Female; Global Health; Humans; Hypertension, Pulmonary; Male; Muscle, Smooth, Vascular; Nitric Oxide; Prostaglandins; Retrospective Studies; Sex Factors; Thrombosis

The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro-thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy.

Topics: Adult; Albuminuria; Antibodies, Antiphospholipid; Anticholesteremic Agents; Anticoagulants; Antioxidants; Antiphospholipid Syndrome; Arachidonic Acids; Creatinine; Endothelin-1; Female; Humans; Lipids; Male; Middle Aged; Nitric Oxide; Pilot Projects; Probucol; Prothrombin; Thrombosis; Thromboxane B2; von Willebrand Factor; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH.. In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and smooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1.. In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A.. Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.

Topics: Chronic Disease; Endarterectomy; Endothelin-1; Humans; Hypertension, Pulmonary; Oxidants; Pulmonary Embolism; RNA, Messenger; Thrombosis

The compounds of Radix Paeoniae Rubra (RPR) were isolated and identified by bioassay-guided method, and antithrombotic effects and mechanism were investigated by the acute blood stasis rat model. The RPR extract was evaluated by APTT, TT, PT, and FIB assays in vitro. Results indicated that RPR extract exhibited the anticoagulant activity. In order to find active compounds, six compounds were isolated and identified, and four compounds, paeoniflorin (Pae), pentagalloylglucose (Pen), albiflorin (Ali), and protocatechuic acid (Pro), exhibited the anticoagulant activity in vitro. Therefore, the antithrombosis effects of RPR extract and four active compounds were investigated in vivo by measuring whole blood viscosity (WBV), plasma viscosity (PV), APTT, PT, TT, and FIB. Meanwhile, the levels of TXB

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Biological Assay; Bridged-Ring Compounds; Drugs, Chinese Herbal; Endothelin-1; Female; Fibrinolytic Agents; Glucosides; Hydrolyzable Tannins; Hydroxybenzoates; Male; Monoterpenes; Nitric Oxide Synthase Type III; Paeonia; Phytotherapy; Rats; Rats, Sprague-Dawley; Thrombosis; Thromboxane B2; Viscosity

Topics: Adult; Antiphospholipid Syndrome; Arginine; Chronic Disease; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Prognosis; Thrombosis; Young Adult

Recent investigations have associated airborne particulate matter (PM) with increased coagulation and thrombosis, but underlying biological mechanisms are still incompletely characterised. DNA methylation is an environmentally sensitive mechanism of gene regulation that could potentially contribute to PM-induced hypercoagulability. We aimed to test whether altered methylation mediates environmental effects on coagulation.. We investigated 63 steel workers exposed to a wide range of PM levels, as a work-related condition with well-characterised prothrombotic exposure. We measured personal PM10 (PM≤10 µm in aerodynamic diameter), PM1 (≤1 µm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitric-oxide-synthase-3) and EDN1 (endothelin-1) through bisulfite-pyrosequencing and we measured ETP as a global coagulation-activation test after standardised triggers.. ETP increased in association with PM10 (β=20.0, 95% CI 3.0 to 37.0), PM1 (β=80.8 95% CI 14.9 to 146.7) and zinc (β=51.3, 95% CI 0.01 to 111.1) exposures. NOS3 methylation was negatively associated with PM10 (β=-0.2, 95% CI -0.4 to -0.03), PM1 (β=-0.8, 95% CI -1.4 to -0.1), zinc (β=-0.9, 95% CI -1.4 to -0.3) and iron (β=-0.7, 95% CI -1.4 to -0.01) exposures. Zinc exposure was negatively associated with EDN1 (β=-0.3, 95% CI -0.8 to -0.1) methylation. Lower NOS3 (β=-42.3; p<0.001) and EDN1 (β=-14.5; p=0.05) were associated with higher ETP. Statistical mediation analysis formally confirmed NOS3 and EDN1 hypomethylation as intermediate mechanisms for PM-related coagulation effects.. Our study showed for the first time, that gene hypomethylation contributes to environmentally induced hypercoagulability.

Topics: Adult; Air Pollutants; Blood Coagulation; Blood Coagulation Disorders; Confidence Intervals; DNA Methylation; Endothelin-1; Gene Expression Regulation; Humans; Industry; Inflammation; Inhalation Exposure; Leukocytes; Male; Middle Aged; Nitric Oxide Synthase Type III; Occupational Diseases; Occupational Exposure; Particulate Matter; Thrombosis; Zinc

In 44 patients with ischemic heart disease (IHD) and 35 healthy subjects we studied cascade mechanism of platelets activation by von Willebrand factor (vWF), and interrelationship of platelet aggregation, level of vWF, and endothelial dysfunction. The latter was estimated by severity of vasoconstriction determined basing on endothelin-1 levels. Quantitative assessment of platelet aggregation revealed differences in aggregation capacity between healthy subjects and patients with IHD. Of particular importance was absence of spontaneous aggregation in healthy subjects. It was shown that in IHD patients influence of vWF resulted in augmentation and convergence of activating signal. Positive correlation was found in patients with IHD between elevation of levels of vWF, endothelin-1, and spontaneous and induced platelet aggregation activity. Interrelationship was revealed between character of IHD course and degree of elevation of the studied markers.

Topics: Biomarkers; Blood Coagulation; Blood Platelets; Endothelin-1; Endothelium, Vascular; Humans; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation; Platelet Function Tests; Prognosis; Statistics as Topic; Thrombosis; von Willebrand Factor

Blood-brain-barrier (BBB) disruption, inflammation and thrombosis are important steps in the pathophysiology of acute ischemic stroke but are still inaccessible to therapeutic interventions. Rolipram specifically inhibits the enzyme phosphodiesterase (PDE) 4 thereby preventing the inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to relief inflammation and BBB damage in a variety of neurological disorders. We investigated the therapeutic potential of rolipram in a model of brain ischemia/reperfusion injury in mice. Treatment with 10mg/kg rolipram, but not 2 mg/kg rolipram, 2 h after 60 min of transient middle cerebral artery occlusion (tMCAO) reduced infarct volumes by 50% and significantly improved clinical scores on day 1 compared with vehicle-treated controls. Rolipram maintained BBB function upon stroke as indicated by preserved expression of the tight junction proteins occludin and claudin-5. Accordingly, the formation of vascular brain edema was strongly attenuated in mice receiving rolipram. Moreover, rolipram reduced the invasion of neutrophils as well as the expression of the proinflammatory cytokines IL-1β and TNFα but increased the levels of TGFβ-1. Finally, rolipram exerted antithrombotic effects upon stroke and fewer neurons in the rolipram group underwent apoptosis. Rolipram is a multifaceted antiinflammatory and antithrombotic compound that protects from ischemic neurodegeneration in clinically meaningful settings.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Brain Injuries; Cytokines; Disease Models, Animal; Encephalitis; Endothelin-1; Hemodynamics; Infarction, Middle Cerebral Artery; Laser-Doppler Flowmetry; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Occludin; Phosphodiesterase 4 Inhibitors; Rolipram; Stroke; Thrombosis

Arteriovenous (AV) graft is frequently used as vascular access in hemodialysis patients. However, clotting or thrombosis of AV grafts often occurs and requires surgical removal. At present, the molecular pathogenesis underlying thrombosis of AV graft is not clear. The PTEN/Akt signaling has been implicated in the pathogenesis of vascular diseases. In this study, elevated PTEN expression and concomitant Akt inactivation was observed in endothelium of atherosclerotic brachial arteries from hemodialysis patients. To investigate whether PTEN upregulation affects endothelial function, adenovirus-mediated PTEN (Ad-PTEN) overexpression was performed in aorta rings and cultured endothelial cells. It was found that PTEN overexpression potently inhibited the microvessel sprouting in aorta rings and the angiogenic activities of endothelial cells including migration and tube formation. On the contrary, PTEN knockdown by RNA interference promoted the endothelial migration and reversed the Ad-PTEN-induced inhibition of endothelial migration. Expression analysis showed that PTEN overexpression attenuated the expression of endothelin-1 (ET-1) and endothelin B receptor (ETBR) in endothelial cells at transcriptional levels. However, exogenous ET-1 supply only partially reversed the PTEN-induced inhibition of migration and tube formation. This was delineated due to that PTEN overexpression also perturbed endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) release. In summary, PTEN upregulation induces endothelial dysfunction by attenuating the availability and signaling of multiple angiogenic pathways in endothelial cells, thereby may contribute to thrombosis of AV graft.

Topics: Animals; Arteriovenous Shunt, Surgical; Cell Movement; Endothelial Cells; Endothelin-1; Enzyme Activation; Graft Occlusion, Vascular; HEK293 Cells; Human Umbilical Vein Endothelial Cells; Humans; Male; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; Phosphorylation; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Rats; Rats, Sprague-Dawley; Receptor, Endothelin B; Renal Dialysis; RNA Interference; Signal Transduction; Thrombosis; Tissue Culture Techniques; Transcription, Genetic; Transfection; Up-Regulation; Vascular Endothelial Growth Factor A

Plaque rupture and subsequent embolism as well as thrombosis are major causes of acute myocardial infarction and stroke secondary to atherosclerosis. Pai-1, t-PA, TF and ET-1 are thrombosis- and thrombolysis-related factors which play important roles in thrombosis formation and plaque rupture. Since acute myocardial infarction and stroke are more likely to occur between 6 a.m. and 12 p.m. than at another time of the day, we studied the relationship between circadian rhythm and Pai-1, t-PA, TF and ET-1 in normal and atherosclerotic mice. Atherosclerosis was developed in apoE-/- mice fed a normal diet or a high cholesterol diet. The expression of Pai-1, t-PA, TF and ET-1 in the hearts of control C57BL/6J mice and atherosclerotic mice was measured by real-time RT-PCR at different Zeitgeber times (ZT) including ZT0, ZT4, ZT8, ZT10, ZT12, ZT14, ZT16 and ZT20. The expression of Pai-1, t-PA, TF and ET-1 peaked between ZT14 and ZT16 and bottomed at ZT10 in C57BL/6J mice. Their expression in apoE-/- mice fed a normal diet lost circadian rhythm. Their expression in apoE-/- mice fed a high cholesterol diet peaked at ZT4, indicating a reverse circadian rhythm. Our result indicates that circadian changes in the expression of Pai-1, t-PA, TF and ET-1 may be involved in the onset of myocardial infarction and stroke.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Cholesterol, Dietary; Chronobiology Disorders; Circadian Rhythm; Endothelin-1; Gene Expression; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Plasminogen Activator Inhibitor 1; Thromboplastin; Thrombosis; Tissue Plasminogen Activator

The aim of this study was to evaluate traditional risk factors for coronary artery disease (CAD), homocysteine, anti-oxidized low-density lipoprotein (anti-oxLDL), anti-lipoprotein lipase (anti-LPL) and endothelin-1 (ET-1) in patients with primary anti-phospholipid syndrome (APS), furthermore verify possible association among these variables and arterial thrombosis. Thirty-eight women with primary APS and 30 age-and-sex-matched controls were evaluated. Patients presented higher-LDL and triglycerides levels and lower-HDL levels than controls. Anti-LPL antibodies were not detected in both groups. The mean number of risk factors was higher in patients than in controls (P = 0.030). Anti-oxLDL antibodies, homocysteine and ET-1 mean levels were similar between groups, but abnormal homocysteine levels were found only among primary APS patients (P = 0.031). Hypertension and the presence of at least one risk factor for CAD were more prevalent in patients with arterial involvement than those without. Homocysteine levels and mean number of risk factors for CAD were significantly higher in patients with arterial thrombosis than controls. In a multivariate analysis hypertension was the only independently associated with arterial thrombosis (OR 14.8, 95% CI = 2.1-100.0, P = 0.006). This study showed that in primary APS patients other risk factors besides anti-phospholipid antibodies contribute for the occurrence of arterial events and the most important factor was hypertension.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoantibodies; Case-Control Studies; Coronary Artery Disease; Endothelin-1; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Lipoprotein Lipase; Lipoproteins, LDL; Middle Aged; Risk Factors; Thrombosis

In the uncomplicated course of myocardial infarction (MI), the level of endothelin-1 (ET-1) comes to be increased beginning from day 1 and remains the same during the acute phase of the disease and gets decreased during the subacute phase. In MI presenting with parietal thrombosis, left ventricular aneurism, the level of ET-1 increases during the first period of 24 hours, increasing further toward the end of the acute phase, there being no decrease in the subacute phase. In MI presenting with pericardial effusion, an increase in the level of ET-1 is seen during the first period of 24 hours of the disease with no rise being recordable in peptide concentration during the acute and subacute phases. There is a positive correlation between the level of ET-1 and size of the heart cavities in the systole and diastole, pressure in the pulmonary artery, and a negative one with indices for the systolic function.

Topics: Endothelin-1; Female; Heart Aneurysm; Humans; Male; Middle Aged; Myocardial Infarction; Pericardial Effusion; Thrombosis

To evaluate the mechanisms of thrombosis in the early stage of electrical injury.. Endothelin-1(ET-1), prostacylin(PGI2), platelet alpha-granule membrane protein (Gmp-140), thromboxane (TXB2), and plasminogen(PLG-A) were measured in 26 patients with electrical injury.. It was found that GMP-140 and ET-1 increased significantly(P < 0.01), PLG-A showed a significant change 2 weeks after the injury, while there was an imbalance between TXB2 and PGI2.. It is believed that change in one or several mediators mentioned above may trigger thrombosis after electrical injury.

Topics: Adolescent; Adult; Burns, Electric; Endothelin-1; Epoprostenol; Female; Humans; Male; Middle Aged; P-Selectin; Thrombosis; Thromboxane B2

To explore a possible correlation between endothelin 1 (ET-1), the most potent endothelium-derived contracting factor that modulates vascular smooth muscle tone, and arterial disease in patients with the antiphospholipid syndrome (APS).. Plasma levels of ET-1 were measured in APS patients with (n = 16) and without (n = 11) arterial thrombosis and in non-APS patients with arterial thrombosis (n = 9). In addition, steady-state prepro-ET-1 messenger RNA (mRNA) levels were determined in endothelial cells treated with a range of human monoclonal anticardiolipin antibodies (aCL) (as anti-beta2-glycoprotein I antibodies) by semiquantitative 32P-dCTP-labeled reverse transcription-polymerase chain reaction.. Compared with healthy controls, markedly increased plasma levels of ET-1 were found in APS patients with arterial thrombosis (2.00 +/- 0.87 versus 0.96 +/- 0.37 pg/ml; P = 0.0001) but not in other groups. Three human monoclonal aCL induced prepro-ET-1 mRNA levels significantly more than did control monoclonal antibody lacking aCL activity.. Plasma ET-1 levels correlated significantly with a history of arterial thrombosis in patients with APS. Prepro-ET-1 mRNA was induced by human monoclonal aCL in the in vitro experimental system. The induction of ET-1 by antiphospholipid antibodies might contribute to increased arterial tone, leading to vasospasm and, ultimately, to arterial occlusion.

Topics: Adult; Antibodies, Anticardiolipin; Antibodies, Monoclonal; Antiphospholipid Syndrome; Arterial Occlusive Diseases; beta 2-Glycoprotein I; Cells, Cultured; DNA Primers; Endothelin-1; Endothelins; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Male; Middle Aged; Polymerase Chain Reaction; Protein Precursors; RNA, Messenger; Thrombosis

Thrombolytic therapy is frequently used to manage vascular graft thrombosis. However, long-term patency after thrombolysis remains poor. The purpose of this study was to characterise the morphological and functional response of endothelial cells (EC) exposed to a thrombus and subsequently lytic therapy.. Human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h. The thrombus was lysed with urokinase. Cell morphology was studied with electron microscopy. Northern blot analyses were performed with human c-DNA probes for endothelin-1, thrombomodulin, tissue factor, tissue plasminogen activator, plasminogen activator inhibitor, and triose phosphate isomerase.. EC retraction occurred for each period of incubation. Thrombomodulin expression was increased 2.2-fold at 6 h and 2.4-fold at 24 h. t-PA expression was depressed proportionally to the duration of thrombus exposure. PAI and TF expression transiently increased 1.5-fold at 2 h of exposure and returned to baseline at 6 h. Endothelin expression remained unchanged.. Except for a transient increase in TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus do not appear to become actively procoagulant. The increase in TM expression may reflect enhanced thromboresistance. However, EC retraction may be responsible for an increase thrombogenicity of saphenous vein graft after thrombosis and Urokinase therapy.

Topics: Cells, Cultured; Endothelin-1; Endothelium, Vascular; Graft Occlusion, Vascular; Humans; Microscopy, Electron, Scanning; Plasminogen Activator Inhibitor 1; Saphenous Vein; Thrombolytic Therapy; Thrombomodulin; Thromboplastin; Thrombosis; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10. One attractive theory links ubiquinone with the inhibition of platelets. The effect of CoQ10 intake on platelet surface antigens, and certain hemostatic parameters was examined in 15 humans and 10 swine. Study participants received 100 mg of CoQ10 twice daily in addition to their usual diet for 20 days resulting in a three-fold increase of total serum CoQ10 level. We observed a decline in plasma fibronectin (-20.2%), thromboxane B2 (-20.6%), prostacyclin (-23.2%), and endothelin-1 (-17.9%) level. Significant inhibition of vitronectin receptor expression was observed consistently throughout ubiquinone treatment. Inhibition of the platelet vitronectin receptor is a direct evidence of a link between dietary CoQ10 intake, platelets, and hemostasis. These findings may contribute to the observed clinical benefits by a diminished incidence of thrombotic complications in such patients.

Topics: Animals; Coenzymes; Down-Regulation; Endothelin-1; Epoprostenol; Female; Fibronectins; Hemostasis; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Receptors, Vitronectin; Swine; Thrombosis; Thromboxane B2; Ubiquinone

We previously showed that endothelin-1 (ET-1) causes accumulation of leukocytes in the pulmonary microvasculature and increases vascular permeability in isolated rat lungs provided the presence of leukocytes in the perfusate. In the present study, we examined the time sequence for morphological changes induced by ET-1 in rat alveolar tissue. For this purpose we used morphometric analysis based on lung transmission electron micrographs. Morphometry was performed by point counting, and data were expressed as relative volume density. ET-1 (0.06, 0.6, and 6 nmol/kg) was infused into the internal jugular vein, and the animals were killed at certain points of time. The lungs were fixed by endotracheal instillation of McDowell's fixative. Infusion of ET-1 (0.06 or 0.6 nmol/kg) caused no significant morphological changes in the rat alveolar tissue as assessed by morphometric examination. A sevenfold increase in volume density of platelets was seen 5 min after infusion of ET-1 6 nmol/kg. The platelets were loosely aggregated, adhered partly to the endothelium, and some of them had a spherical shape with vacuoles, indicating activation. The volume density of erythrocytes increased threefold, lasting 30 min. At 120 min, the volume density of polymorphonuclear leukocytes (PMN) increased 10-fold. The PMN adhered closely to the endothelium and partly occluded the capillary lumen. Simultaneously, the endothelial cell surface showed morphological signs of injury. No significant changes were observed in the volume density of alveolar macrophages or monocytes. No significant changes were seen in lung volumes or the volume of the alveolar tissue compartment. The results showed that ET-1 causes a time- and dose-dependent sequential entrapment of platelets and neutrophils in the pulmonary circulation.

Topics: Animals; Blood Platelets; Endothelin-1; Endothelium, Vascular; Male; Microcirculation; Microscopy, Electron; Neutrophils; Platelet Activation; Platelet Aggregation; Pulmonary Alveoli; Pulmonary Circulation; Rats; Rats, Wistar; Thrombosis

Experiments were designed to compare perioperative blood loss, early thrombogenicity and morphologic and functional characteristics of the neointima of three types of prosthetic materials used for carotid artery patch angioplasty. Bilateral carotid patch angioplasties were performed in 20 dogs, using 20 gelatin-impregnated fluoropassivated Dacron (GIF), 10 untreated knitted Dacron and 10 expanded polytetrafluoroethylene (PTFE) patches (5 cm2). Intraoperative blood loss, platelet deposition at 24 h and neointimal morphology at 6 weeks after the operation were assessed. Bioassay of the neointima was performed at 6 weeks in 16 patches. Mean (s.e.m.) blood loss was significantly less in GIF patches (14.7 (2.7) ml) compared with either PTFE (75.6 (24) ml) or untreated Dacron (64.3 (9.5)) (P < 0.005). Mean (s.e.m.) platelet deposition in GIF patches (1380 (328) platelets/cm2) was approximately 50% less at 24 h than in untreated Dacron (2562 (1035) platelets/cm2) or PTFE (2140 (998( platelets/cm2) patches (P < 0.05). Neointimal coverage was greater in PTFE (94 (1.3%)) compared with GIF (79 (2.7%)) or untreated Dacron (86 (2.4%)) patches (P < 0.05). The thickness of the neointimal layer of PTFE (0.5 (0.01) mm) patches was greater than other patch types; GIF (0.2 (0.01) mm) or untreated Dacron (0.3 (0.01) mm) (P < 0.50). Under bioassay conditions, acetylcholine caused release of vasoactive relaxing factor(s) from all patches. However, relaxations from baseline were less with GIF patches (-37.9 (11.7)% versus -54.5(9.6( for untreated Dacron; -50.2 (15.2)% for PTFE) (P = n.s.). Endothelin-1 release occurred from all patches and was increased with the extent of neointimal coverage. These data demonstrate that GIF patches caused the least perioperative bleeding, were the least thrombogenic at 24 h and developed the thinnest neointima at 6 weeks. All patch materials developed a functioning neointima.

Topics: Angioplasty; Animals; Biocompatible Materials; Blood Vessel Prosthesis; Carotid Arteries; Dogs; Endothelin-1; Evaluation Studies as Topic; Gelatin; Platelet Aggregation; Polyethylene Terephthalates; Polytetrafluoroethylene; Postoperative Complications; Postoperative Hemorrhage; Thrombosis; Tunica Intima; Vascular Patency