Effect of prostacyclin on pulmonary vascular response to thrombin in awake sheep

1986 ◽  
Vol 60 (2) ◽  
pp. 546-553 ◽  
Author(s):  
M. B. Perlman ◽  
S. K. Lo ◽  
A. B. Malik

We determined the effects of infusion of prostacyclin (PGI2) and 6-alpha-carba-PGI2 (6-cPGI2), a stable PGI2 analogue, on pulmonary transvascular fluid and protein fluxes after intravascular coagulation induced by thrombin. Studies were made in control awake sheep prepared with lung lymph fistulas (n = 6) and in similarly prepared awake sheep pretreated with either 6-cPGI2 (n = 5) or PGI2 (n = 5). Both prostacyclin compounds (500 ng X kg-1 X min-1) were infused intravenously. All groups were challenged with 80 U/kg thrombin. Pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), pulmonary lymph flow (Qlym), lymph protein clearance (Qlym X lymph/plasma protein concentration ratio), and neutrophil and platelet counts were determined. In vitro tests assessed sheep neutrophil chemotaxis and chemiluminescence and platelet aggregation. In both 6-cPGI2 and PGI2 groups, the increases in Qlym after thrombin were less than those in the control group. The increase in lymph protein clearance in the 6-cPGI2 group was the same as that in control, whereas the increase in clearance in the PGI2 group was reduced. PVR and Ppa increased to a greater extent in the 6-cPGI2 group than in the control group, whereas the increases in PVR and Ppa were inhibited in the PGI2 group. Neutrophil and platelet counts decreased after thrombin in PGI2 and 6-cPGI2 groups, as they did in the control group. Neither 6-cPGI2 altered neutrophil chemotaxis induced by thrombin and chemiluminescence induced by opsonized zymosan. Both prostacyclin compounds inhibited platelet aggregation induced by ADP or thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

1981 ◽  
Author(s):  
A B Malik ◽  
F L Minnear ◽  
M V Tahamont ◽  
D G Moon ◽  
J E Kaplan

We determined the effects of ADP-induced platelet aggregation on lung fluid and protein exchange to examine whether platelet aggregation mediates lung vascular injury. The studies were made in intact sheep in which pulmonary lymph was obtained, and the protein concentration of lymph was compared to that of plasma. Two groups were studied: Control sheep receiving i.v. infusion of 10 mg/kg of ADP and experimental sheep in which platelets were depleted with anti-platelet serum prior to ADP infusion. In the control group, ADP decreased the platelet count from 178,554 ± 62,750 to 103,500 ± 47,828 cells/mm3, suggesting the entrapment of platelet in the pulmonary circulation. The pulmonary arterial pressure (Ppa) increased from 13.1 ± 1.8 to 15.9 ± 1.2 mmHg. Lung lymph flow (Qlym) increased from 8.4 ± 1.8 to 11.4 ± 2.3ml/hr (p < 0.05) and transvascular protein clearance (Qlym x lymph/plasma protein concentration), a measure of protein exchange, increased from 6.7 ± 1.3 to 9.4 ± 3.0 ml/hr (p < 0.05). These increases could be explained by an increase in microvascular pressure (Pmv) and ultrafiltration since mechanically elevation of Pmv produced the same changes in Qlym and clearance. Platelet depletion prevented the ADP-induced increases in platelet aggregation does not mediate lung vascular injury, but increases fluid filtration by increasing the microvascular pressure. This effect may be mediated by release of pulmonary vasoconstrictor substances such as thromboxane A2 and serotonin after platelet aggregation.


1987 ◽  
Vol 62 (3) ◽  
pp. 863-869 ◽  
Author(s):  
A. Johnson ◽  
S. K. Lo ◽  
F. B. Blumenstock ◽  
A. B. Malik

We examined the effects of cobra venom factor (CVF) on the changes in pulmonary hemodynamics and transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in unanesthetized sheep prepared with lung lymph fistulas. The animals received tranexamic acid (100 mg) to suppress fibrinolysis and were then challenged with an intravenous infusion of alpha-thrombin (80 U/kg). Control-thrombin challenged sheep were compared with the CVF-treated sheep challenged with the same thrombin dosage. CVF treatment (187 U X kg-1 X day-1 for 4 days) decreased the total hemolytic complement activity by 45% of control. Thrombin infusion in control sheep increased the mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and lymph protein clearance (pulmonary lymph flow X lymph-to-plasma protein concentration ratio, Clym). Thrombin infusion in CVF-treated sheep produced smaller increments in Ppa, PVR, and Clym. Pulmonary lymph obtained from control-thrombin and CVF-thrombin sheep induced migration of granulocytes obtained from normal unchallenged sheep. The granulocytes obtained from CVF-treated sheep responded relatively less to the migratory and O-2-generating stimuli (i.e., zymosan-treated serum, pulmonary lymph from sheep after thrombin challenge, and plasma from sheep after CVF treatment) compared with normal granulocytes. The attenuation of the thrombin-induced increases in Ppa, PVR, and lung transvascular fluid and protein exchange by CVF treatment may be the result of impaired function of granulocytes.


1990 ◽  
Vol 68 (3) ◽  
pp. 1260-1264 ◽  
Author(s):  
C. A. Burgess ◽  
B. K. McCandless ◽  
J. A. Cooper ◽  
A. B. Malik

We examined the role of circulating granulocytes in the pulmonary microvascular response to leukotriene B4 (LTB4) by prior depletion of circulating granulocytes using hydroxyurea. LTB4 (2 micrograms/kg injection followed by infusion of 2 micrograms/kg over 15 min) produced transient increases in pulmonary arterial pressure and pulmonary vascular resistance, indicating that neutrophils were not required for the pulmonary hemodynamic effects of LTB4. Infusion of LTB4 in granulocyte-depleted sheep also resulted in transient increases in pulmonary lymph flow (QL) with no significant change in the lymph-to-plasma protein concentration ratio (L/P), findings similar to those in control animals. In vitro studies indicated that LTB4 (10(-7) or 10(-9) M) produced a transient adherence of neutrophils to cultured pulmonary artery endothelial monolayers. Maximal responses occurred at 10 min after the addition of LTB4 to the endothelial cell-neutrophil coculture system, and the adherence decreased to base line within 60 min. LTB4 infusion in sheep also produced a transient uptake of autologous 111In-oxine-labeled neutrophils. The results indicate that LTB4-mediated increase in pulmonary transvascular protein clearance (QL x L/P) is independent of circulating granulocytes.


2019 ◽  
Vol 18 (1) ◽  
pp. 50-54
Author(s):  
S. E. Gostischeva ◽  
N. V. Abzaeva ◽  
E. L. Rakitina ◽  
D. G. Ponomarenko ◽  
M. V. Kostuchenko ◽  
...  

Research objective–studying of a possibility of application antigen – stimulated cellular in vitro tests and technology of the cytometric analysis for control of immunogene activity of batches of vaccine plague live.Materials and methods.As biomodels used white laboratory mice, immunized commercial medicine of vaccine of the plague NIIEG line, live from a strain of Yersinia pestis EV, in doses – 8 х 102, 4 х 103, 2 х 104 and 1 х 105 of living microbic cells. Blood for a research was taken from intact mice and on 7, 14 and 21 days after immunization. The intensity of an antigenreaktivnost of lymphocytes was defined in cellular in vitro tests, analyzing a marker of early activation (CD45+CD3+CD25+) of lymphocytes with use of the monoclonal antibodies conjugated from fluorokhroma. As specific antigen used a complex of water-soluble antigens of a plague microbe.Results.As a result of a research it is shown that at the animals vaccinated by doses 4 х 103 – 1 х 105 living microbic cells, the highest level of an expression activation marker lymphocytes at anti-gene stimulation of in vitro is registered on 14 days after immunization, at the same time the quantity of CD25 – positive lymphocytes are on average 6.8 times higher, than in control group. High degree of direct link (coefficient of correlation of r = 1,000) quantities of the survived animals with increase in level of lymphocytes, expressiruyushchy markers of early activation – CD25 is established.Conclusions.The offered technique can be used as the additional test when studying degree of immunogenicity of new (kandidatny) vaccines against plague.


2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Maciej Dobrzynski ◽  
Magdalena Pajaczkowska ◽  
Joanna Nowicka ◽  
Aleksander Jaworski ◽  
Piotr Kosior ◽  
...  

In the article has been presented an analysis of susceptibility of selected dental materials, made in the CAD/CAM technology. The morphology and structural properties of selected dental materials and their composites were determined by using XRPD (X-ray powder diffraction) techniques, as well as the IR (infrared) spectroscopy. Moreover, an adhesion as well as development of biofilm by oral microorganisms has been studied. It has been shown that a degree of the biofilm development on the tested dental materials depended on microorganism genus and species. Streptococcus mutans has demonstrated the best adhesion to the tested materials in comparison with Candida albicans and Lactobacillus rhamnosus. However, the sintered materials such as IPS e.max® and the polished IPS e.max® have showed the best “anti-adhesive properties” in relation to S. mutans and L. rhamnosus that have not formed the biofilm on the polished IPS e.max® sample. Furthermore, S. mutans have not formed the biofilm on both surfaces. On the contrary to S. mutans and L. rhamnosus, C. albicans has demonstrated the adhesive properties in relation to the above-mentioned surfaces. Moreover, in contrast to S. mutans and C. albicans, L. rhamnosus has not formed the biofilm on the polished IPS Empress material.


2004 ◽  
Vol 92 (07) ◽  
pp. 89-96 ◽  
Author(s):  
David Payne ◽  
Chris Jones ◽  
Paul Hayes ◽  
Sally Webster ◽  
A. Naylor ◽  
...  

SummaryThe majority of patients who suffer peri-operative thromboembolic complication while undergoing vascular procedures do so despite taking aspirin. This study examined the antiplatelet effect of aspirin during surgery in patients undergoing carotid endarterectomy (CEA). Fifty patients undergoing CEA were standardised to 150 mg aspirin daily for ≥2 weeks. Platelet aggregation in response to arachidonic acid (AA) was measured in platelet rich plasma prepared from blood taken prior to, during, and at the end of surgery. Spontaneous platelet aggregation was also studied, as was the role of physiological agonists (ADP, collagen, thrombin, and epinephrine) in mediating the in vivo and in vitro responses to AA. Eighteen patients undergoing leg angioplasty, also on 150 mg aspirin, without general anaesthesia, served as a control group. In the CEA patients aggregation induced by AA (5 mM) increased significantly from 7.6 ± 5.5% pre-surgery to 50.8 ± 29.5% at the end of surgery (p <0.0001). Aggregation to AA was even greater in samples taken mid-surgery from a sub-set of patients (73.8 ± 7.2%; p = 0.0001), but fell to 45.9 ± 7.4% by the end of surgery. The increased aggregation in response to AA was not due to intra-operative release of physiological platelet agonists since addition of agents that block/neutralise the effects of ADP (apyrase; 4 µg/ml), thrombin (hirudin; 10 units/ml), or epinephrine (yohimbine; 10 µM/l) to the samples taken at the end of surgery did not block the increased aggregation.The patients undergoing angioplasty also showed a significant rise in the response to AA (5 mM), from 5.6 ± 5.5% pre-angioplasty to 32.4 ± 24.9% at the end of the procedure (p <0.0001), which fell significantly to 11.0 ± 8.1% 4 hours later. The antiplatelet activity of aspirin, mediated by blockade of platelet arachidonic acid metabolism, diminished significantly during surgery, but was partially restored by the end of the procedure without additional aspirin treatment.This rapidly inducible and transient effect may explain why some patients undergoing cardiovascular surgery remain at risk of peri-operative stroke and myocardial infarction.


1986 ◽  
Vol 60 (1) ◽  
pp. 266-274 ◽  
Author(s):  
F. L. Minnear ◽  
A. Johnson ◽  
A. B. Malik

We determined in anesthetized sheep whether isoproterenol, a beta-adrenergic agonist, prevents the increases in pulmonary fluid and protein exchange produced by thrombin-induced intravascular coagulation. Seven sheep were infused intravenously with 0.05 micrograms X kg-1 X min-1 isoproterenol before infusion of alpha-thrombin, and six sheep were infused with alpha-thrombin only and served as control subjects. The marked increases in pulmonary lymph flow and lymph protein clearance in the control thrombin group were attenuated (P less than 0.05) in the isoproterenol group in association with a higher pulmonary blood flow (P less than 0.05) and a lower pulmonary vascular resistance (P less than 0.05) in the isoproterenol group and with similar increases in pulmonary arterial and pulmonary arterial wedge pressures in both groups. The decreases in fluid and protein fluxes produced by isoproterenol are related to its beta-adrenergic properties because propranolol, a beta-adrenergic antagonist, blocked the protective effects of isoproterenol in a second group of sheep infused with propranolol, isoproterenol, and thrombin. Raising left atrial pressure to test for changes in vascular permeability increased protein flux to a much greater extent in the thrombin control group than in the isoproterenol group challenged with thrombin. The data suggest that isoproterenol attenuated the increase in fluid and protein fluxes produced by thrombin-induced intravascular coagulation by a permeability-decreasing mechanism.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2325-2325
Author(s):  
Mo Yang ◽  
Min Zhou ◽  
Su yi Li ◽  
Beng Chong ◽  
Xiao jing Li

Abstract Thrombocytosis and inflammation cytokines may be involved in the pathogenesis of vasculitis. Our previous study have showed that major inflammation cytokine IL-1β play an important role on in-vitro megakaryopoiesis (Yang M et al, Br J Haematol 2000). In this study, we investigated the changes of IL-1β and megakaryopoiesis and the effect of aspirin in an immune vasculitis model. Rabbit immune vasculitis model was established by intravenous injection of bovine serum albumin. In this model, platelet number and function of periphery blood, megakaryocyte number and the CFU-MK formation of the bone marrow, and serum levels of inflammatory cytokines were investigated. After treatment with BSA for 7 days, the platelet count, platelet aggregation and the expression of AnnexinⅤ were significantly increased in this vasculitis model group compared with normal control group (n=6). The serum levels of inflammatory cytokine IL-1β was also significantly higher in vasculitis model. There were positive correlations between platelet count and IL-1β levels (R=0.55), platelet aggregation and IL-1β levels (R=0.603). Treatment with aspirin (100 mg/kg/d) significantly decreased all these parameters, showing aspirin had anti-platelets and anti-inflammation effects. Our results also demonstrated that megakaryocyte number and the formation of CFU-MK were significantly increased in vasculitis group as compared to those in normal group. Treatment with aspirin significantly reduced the number of megakaryocytes and the formations of CFU-MK in bone marrow in this immune vasculitis model. Our study further demonstrated that IL-1β alone or in combination with TPO induced in-vitro CFU-MK formation. Using RT-PCR techniques, the mRNA of of IL-1 type I and type II receptors (IL-1 RI and RII) were detected in cultured CD61+ CD41+ cells and four megakaryocytic cell lines. The expression of IL-1 RI and RII was also confirmed by flow cytometry and immunofluorescence staining in bone marrow megakaryocytes. Moreover, the IL-1R bloker can reduced IL-1β induced megakaryopoiesis. This sudy showed that IL-1β may play an important role in the pathogenesis of immune vasculitis. Aspirin has anti-inflammation effects in this model which may be mediated via inhibiting megakaryopoiesis and platelet formation. Disclosures: No relevant conflicts of interest to declare.


Plant Disease ◽  
2002 ◽  
Vol 86 (2) ◽  
pp. 186-186
Author(s):  
H. Vintal ◽  
D. Shtienberg ◽  
E. Shlevin ◽  
E. Ben-Noon

Alternaria leaf blight, caused by Alternaria dauci (Köhn) Groves & Skolko, is one of the most devastating foliar pathogens of carrots (Daucus carota L.). Lesions appear as minute, necrotic, dark brown spots often initiated on the edge of the leaflet blade. They later enlarge in size and may merge into a large necrotic area, causing shriveling of the entire leaflet (1). In summer 2000, observations made in several carrot fields in the northwestern part of the Negev Region in Israel revealed infections that were atypical for A. dauci because they were initiated primarily in the middle section of the leaflet blade and were surrounded by a large yellowish area. A. longipes (Ellis & Everh.) E. Mason was consistently isolated from the lesions. Occasionally both A. longipes and A. dauci developed on the same leaves. The two pathogens differed in conidial morphology (size and shape of spore and beak) when cultured on potato dextrose agar medium. One hundred conidia of each species were measured. A. dauci conidia were 100 to 450 μm long and 6 to 15 μm wide, with a beak of up to 3 times the length of the conidium; A. longipes conidia were 35 to 110 μm long and 11 to 21 μm wide, and the beak measured one-third to one-half the length of the conidium. These measurements corresponded to the sizes listed previously (2). Inoculation of greenhouse-grown plants and completion of Koch's postulates confirmed that A. longipes is pathogenic to carrots. Conidia of both species germinated at temperatures from 5 to 36°C. In vitro tests revealed that A. longipes was less sensitive than A. dauci to fungicides commonly used in Israel in carrot fields. A fifty percent effective dose of chlorothalonil and difenoconazole was 3.0 and 0.2 μg a.i./ml, respectively, for mycelia growth of A. dauci, whereas the corresponding values for A. longipes were 10.5 and 3.0 μg a.i./ml, respectively. The prevalence of A. longipes in carrot fields and the influence of this pathogen on yields are currently not known. References: (1) I. Barash et al. Physiol. Plant Pathol. 19:7, 1981. (2) M. B. Ellis. Dematiaceous Hyphomycetes. CMI. Kew, Surrey, England, 1971.


Author(s):  
Esra Yazarlı ◽  
Pınar Işık Ağras ◽  
Yildiz Dallar ◽  
Bulent Alioglu

Abstract Aim: This study aimed to investigate the in-vitro platelet aggregation and secretion tests in children patients with Henoch-schöenlein Purpura that recently referred to as Ig A vasculitis Methods: This is a cross-section study that included 55 patients with Henoch-schöenlein Purpura and 31 healthy children as a control group. Children who have a history of drug use, chronic diseases, and bleeding diseases were excluded from the study. Complete blood count, thrombocyte aggregation, and secretion tests were studied in both groups. These tests were re-evaluated in remission of the disease. Results: It was found that epinephrine-stimulated platelet aggregation and collagen, epinephrine, ristocetin, arachidonic acid, standard dose thrombin, and high dose thrombin-stimulated platelet secretion results were lower in the patients with Henoch-schöenlein Purpura compared to the healthy control group in the acute period (respectively P=0.014, 0,003; 0,003; 0,027; 0,034; 0,010; 0,049). When the values of patients with Henoch-schöenlein Purpura in the acute period and the remission of the disease were compared, collagen-stimulated platelet aggregation and epinephrine-stimulated platelet secretion values were found to be lower in patients with patients in the acute period (P= 0.016; 0.039) Conclusion: Impairment in vitro platelet aggregation and secretion tests in the patients with Henoch-schöenlein Purpura suggest that the tendency to bleeding in these patients may be due to platelet impairment function. Key Words: Henoch-schöenlein Purpura, platelet aggregation tests, platelet secretion tests, children, Ig A vasculitis. What’s already known about this topic? There is a tendency to bleeding in Henoch Shcöenlein Purpura patients, such as gastrointestinal bleeding, nonthrombocytopenic system purpura. What does this article add? It was found that impairment in-vitro platelet aggregation and secretion tests in Henoch Shcöenlein Purpura patients.


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