Platelet Aggregation Rate Research Articles

Effects of different doses of ticagrelor on platelet aggregation and endothelial function in diabetic patients with stable coronary artery disease

We performed this study to observe the effects of different doses of ticagrelor and standard-dose clopidogrel on platelet reactivity and endothelial function in diabetic patients with stable coronary artery disease (CAD). Sixty type 2 diabetic patients were assigned to one-quarter standard-dose ticagrelor, half standard-dose ticagrelor, standard-dose ticagrelor and standard-dose clopidogrel groups. Light transmission aggregometry (LTA) and VerifyNow assay were used to measure platelet function. Endothelial function was assessed by measurement of flow-mediated vasodilation (FMD) and plasma von Willebrand factor (VWF) levels were detected. Enzyme-linked immunosorbent assay (ELISA) examined the Interleukin-8(IL-8) and IL-10. The results suggested that the one-quarter dose (34.0%± 14.7%), half-dose (26.9%± 11.6%) and standard-dose (17.3%± 10.3%) ticagrelor showed lower platelet aggregation rate than clopidogrel (52.8%± 18.3%; P ＜0.0001). PRU values in three ticagrelor groups were lower than that in clopidogrel group (102 (76–184)；75 (33–88)；38 (11–52) versus 194 (138–271) and；P ＜0.0001). FMD levels were higher in ticagrelor groups compared with baseline levels while lower in clopidogrel group after treatment. However, no significant differences were found in the percentage increase in the FMD between ticagrelor groups and clopidogrel group. The levels of VWF after treatment were lower than the baseline levels, but there was no statistically significant difference between ticagrelor group and clopidogrel group after treatment. The concentration of IL-8 and IL-10 were decreased in patients with half and standard-dose ticagrelor group. In conclusion, one-quarter standard-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose clopidogrel in diabetic patients with stable CAD. The half standard-dose ticagrelor had a similar inhibitory effect on platelet inhibition as standard-dose ticagrelor, which was stronger than that of clopidogrel. Moreover, the half-dose ticagrelor had equal protection of endothelial function and inhibition of inflammatory factor as standard-dose ticagrelor.

Hypermucoviscous Klebsiella pneumoniae infections induce platelet aggregation and apoptosis and inhibit maturation of megakaryocytes

IntroductionDifferent Klebsiella pneumoniae strains carry different virulence factors and antibiotic resistance and may cause thrombocytopenia. This study aimed to investigate the effects of different infections caused by K. pneumoniae on platelets. MethodsTwo hypermucoviscous K. pneumoniae strains and two classic strains were collected from clinical blood culture, and in both groups, there was a carbapenem-resistant strain and a carbapenem-sensitive strain. Mouse infection models were constructed by intraperitoneally injecting different strains, and mice injected with phosphate-buffered saline served as a control. Count, aggregation rate and apoptosis proportion of platelets within 12 h were examined. CD41 expression was measured in bone marrow cells to determine the maturation of megakaryocytes. The concentrations of lipopolysaccharides and related signaling molecules were also measured. ResultsThe platelet aggregation rate was much significantly higher in the two hypermucoviscous groups, while it showed no difference in the classic groups compared to the control group. All infections induced apoptosis of platelets, among which the highest apoptosis proportions were observed in infections caused by the hypermucoviscous carbapenem-sensitive strain. In both hypermucoviscous groups the CD41 mean fluorescence intensity was much lower than that in the control group, indicating that the maturation of megakaryocytes in the hypermucoviscous groups was significantly inhibited. Lipopolysaccharides were significantly higher and TLR4/Myd88 and JNK/MAPK pathways were strongly activated in hypermucoviscous groups. ConclusionsThe results indicate that hypermucoviscous K. pneumoniae can reduce platelet count by several pathways. Although antibiotic resistance is rapidly emerging worldwide, it has little influence on the decrease in platelets.

Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI.

The effects of different cytochrome P450 2C19 (CYP2C19) genotypes on the prognosis of clopidogrel resistance in patients complicated with atrial fibrillation taking clopidogrel after percutaneous coronary intervention (PCI) were investigated. Eighty patients who were complicated with atrial fibrillation and treated with clopidogrel antiplatelet therapy after PCI in Meizhou Hospital Affiliated to Zhongshan University from September 2015 to January 2017 were selected, and divided into two groups according to the CYP2C19 genotype: extensive metabolism (EM) group and poor metabolism (PM) group. The related risk factors of clopidogrel resistance were determined, and the platelet aggregation rate and clopidogrel resistance rate were compared between the two groups during treatment. Non-fatal myocardial infarction and serious life-threatening complications in the two groups were observed. The increased total cholesterol level and the history of smoking and drinking were the independent risk factors of atrial fibrillation after PCI. The platelet aggregation rates in the EM group at 1, 3 and 12 months after medication were significantly lower than those in the PM group in the same period (P<0.05). The clopidogrel resistance rates in EM group before medication and at 1, 3 and 12 months after medication were higher than those in PM group in the same period (P<0.05). The onset time of non-fatal myocardial infarction in EM group was earlier than that in PM group (P<0.05), the infarct area was larger than that in PM group (P<0.05), and the left ventricular ejection fraction (EF) after onset was lower than that in PM group (P<0.05). In conclusion, the increased total cholesterol level and the history of smoking and drinking are the independent risk factors of clopidogrel resistance in patients complicated with atrial fibrillation after PCI. The incidence rates of cardiac complications are increased significantly in patients with PM CYP2C19 genotype.

Expression of COX-1 and COX-2 in the Platelet of Iron Deficiency Anemia Women at Childbearing Age and Its Clinical Significance

To detect the expression level of cyclooxygenase-1（COX-1） and cyclooxygenase-2（COX-2） in the platelet of iron deficiency anemia（IDA）women at childbearing age and to explore its correlation with the different indexes of anemia and platelets. Forty female IDA patients at childbearing age and 35 healthy controls were enrolled in this study. The Flow cytometry was used to detect the expression of platelet COX-1 and COX-2，the platelet aggregation function as examined by turbidimetric method，and the levels of serum ferritin were analyzed by electrochemical luminescence method，the leval of serum iron was determined by ELISA，and the correlation of different indexes was analyzed. Compared with healthy controls，the levels of platelet COX-1 and COX-2 were significantly lower in female IDA patients at Childbearing age（P<0.05），but platelet count（Plt），mean platelet volume（MPV） and platelet aggregation rate（PAgT）were not statistically different between the 2 groups（P > 0.05）. The expression level of platelet COX-1 positively correlated with those of Hb（r =0.623，P<0.01），serum iron（r =0.321，P<0.05） and HCT（r=0.305，P<0.05）. but the platelet COX-2 expression did not corelate with these indexs. The expression of platelet COX-1 and COX-2 in female IDA patients at Childbearing age markedly decrease，and the expression level of platelet COX-1 closely relates with the severity of anemia，that possesses reference value for clinical diagnosis of female IDA patients at Childbearing age..

The impact of night-shift work on platelet function in healthy medical staff.

Objectives: Rotating shift work has been reported to increase the risk of cardiovascular diseases. Vascular endothelial dysfunction and platelet activation are among the leading causes of thrombus formation in patients with myocardial infarction or stroke. Endothelial function has been shown to be impaired immediately after night-shift work; however, it is not known whether platelets are also activated. The aim of this study was to investigate the acute impact of night-shift work on platelet function. Methods: This observational study included 11 healthy medical staff members (seven women, median age 32 years). We examined each subject's platelet aggregation rates and the serum concentrations of eicosanoid mediators after night-shift work and on day-shift work without preceding night-shift work (baseline). Results: Platelet aggregation did not differ from baseline levels after night-shift work. However, serum cyclooxygenase (COX)-metabolized eicosanoid mediators, particularly thromboxane (Tx) B2 (a stable metabolite of TxA2 and the most important marker of platelet activation), were significantly higher after the night-shift than at baseline (median 65.3 vs 180.4 ng/ml). Conclusions: Although platelet aggregation did not increase, there was an increase in serum COX-metabolized eicosanoid mediators such as TxB2 in healthy medical staff after night-shift work. This platelet hypersensitivity may be one of the mechanisms underlying the significant association between night-shift work and adverse cardiovascular outcomes.

Changes in the functional activity of thrombocytes in rats with experimental disruption of the periodontal connective tissue

Objective . The aim was to study the functional activity of platelets in periodontitis. Materials and methods. Experiments were performed on 20 white nonlinear male rats weighing 320.0 ±30.0 g. Experimental periodontitis was modeled by the method of L. V. Peshkova. Blood for the study of platelet aggregation was taken by a syringe from the heart. Induced platelet aggregation was examined using a Computerized Platelet Aggregation Analyzer SOLAR 2110. Adenosine diphosphate (ADP) was used as an inducer at 2.5 μmol/L and 10.0 μmol/L concentration. The resulting aggregation was recorded at 37 °C for 10 min. Samples of periodontal tissues were fixed in a 10 % neutral-buffered formalin solution, dehydrated in an ascending concentration series of alcohol, followed by chloroform, chloroform-paraffin and embedded into paraffin. Sections 4–6 microns thick were cut on a sliding microtome and stained with hematoxylin-eosin and van Gieson’s stain. Results. Analysis of aggregograms revealed a decrease in the functional activity of platelets in rats with experimental periodontitis at aggregation inducer concentrations of 2.5 μmol/L and 10.0 μmol/L. Reduction in the degree of platelets aggregation and aggregation rate were observed at an inductor concentration of 2.5 μmol/L in a group of rats with experimental periodontitis in comparison with the control. Microscopic examination showed a violation of the connective periodontal tissue histoarchitectonic. Dilatation of small capillaries in the connective tissue layers and in some preparations microvascular congestion were observed which indicated a violation of blood microcirculation, failure of repair regulatory mechanisms and the pathological process’s reaching the systemic level. The interaction of connective tissue cells with platelets played a significant role in these processes. Conclusions. Decrease in thrombocytes aggregation activity is observed in rats with experimental periodontitis. Changes in the periodontal connective tissue manifested by the vascular pattern transformation, microcirculation violations, disruption of repair regulatory mechanisms and the pathological process’s reaching the systemic level.

Ginsenoside-Rp3 inhibits platelet activation and thrombus formation by regulating MAPK and cyclic nucleotide signaling

Background & purposeGinseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. MethodsThe in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca2+]i mobilization, granule secretion, integrin αIIbβ3 activation, and clot retraction were assessed in rat platelets. Its effects on vasodilator-stimulated phosphoprotein (VASP) expression, phosphorylation of MAPK signaling molecules, and PI3K/Akt activation were also studied. Moreover, the tyrosine phosphorylation of components of the P2Y12 receptor downstream signaling pathway was also examined. The in vivo effects of G-Rp3 were studied using an acute pulmonary thromboembolism model and lung histopathology. Key resultsG-Rp3 significantly inhibited collagen, ADP, and thrombin-induced platelet aggregation. G-Rp3 elevated cAMP levels and VASP phosphorylation and suppressed agonist-induced [Ca2+]i mobilization, ATP release, and P-selectin expression along with fibrinogen binding to integrin αIIbβ3, fibronectin adhesion, and clot retraction. G-Rp3 also attenuated the phosphorylation of MAPK, Src, and PLCγ2 as well as PI3K/Akt activation. Furthermore, it inhibited tyrosine phosphorylation of the Src family kinases (Src, Fyn, and Lyn) and PLCγ2 and protected mice from thrombosis. Conclusion and implicationG-Rp3 modulates agonist-induced platelet activation and thrombus formation by inhibiting granule secretion, integrin αIIbβ3 activation, MAPK signaling, and Src, PLCγ2, and PI3K/Akt activation, and VASP stimulation. Our data suggest that G-Rp3 has therapeutic potential as a treatment for platelet-related cardiovascular disorders.

Effects of remote ischemic post-conditioning on platelet activation of AMI patients.

The recovery of ischemic myocardium blood perfusion is the main treatment option for acute myocardial infarction (AMI). However, this treatment option has multiple side effects that directly affect the quality of life of the patients. The activation of platelet function plays an important role in the occurrence, development and treatment of AMI. The aim of the present study was to analyze the effects of remote ischemic post-conditioning on platelet activation of AMI patients with primary PCI treatment and clinical prognosis. A total of 71 patients with AMI were treated with primary percutaneous coronary intervention (PCI). They were randomly divided into control group (n=34) and observation group (n=37). The patients in the observation group were treated with remote ischemic post-conditioning. Further, flow cytometer was used to detect the platelet alpha granule membrane glycoprotein (CD62P) and the percentages of activated IIb/IIIa (PAC-1). The maximum platelet aggregation rate induced by adenosine diphosphate (ADP) and arachidonic acid (AA) was measured by light transmittance aggrometer. The incidence of major adverse cardiac events (MACE) was compared between the two groups during the follow-up period of 6 months. The percentage of CD62P (24 h after PCI) in the observation group was significantly lower than control group (P<0.05). Further, the incidence of MACE in the observation group was also lower than that of the control group (P<0.05). Remote ischemic post-conditioning could reduce the incidence of MACE in patients with AMI after primary PCI treatment. Moreover, the above observation may be related to the improvement of platelet CD62P activation.

Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling.

Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIbβ3 activation, and intracellular calcium ion ([Ca2+]i) mobilization were examined. Western blot analysis and immunoprecipitation techniques were used to estimate the expression of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and interaction of glycoprotein VI (GPVI) signaling pathway molecules such as Src family kinases (SFK), tyrosine kinase Syk, and PLCγ2. In vivo effects were studied using acute pulmonary thromboembolism model in mice. Gintonin remarkably inhibited collagen-induced platelet aggregation and suppressed granule secretion, [Ca2+]i mobilization, and fibrinogen binding to integrin αIIbβ3 in a dose-dependent manner and clot retraction. Gintonin attenuated the activation of MAPK molecules and PI3K/Akt pathway. It also inhibited SFK, Syk, and PLCγ2 activation and protected mice from thrombosis. Gintonin inhibited agonist-induced platelet activation and thrombus formation through impairment in GPVI signaling molecules, including activation of SFK, Syk, PLCγ2, MAPK, and PI3K/Akt; suggesting its therapeutic potential against platelet related CVD.

Effect of Ligustrazine Liposomes on Apoplexy of Focal Cerebral Ischemia in Rats

Objective: To study the efficacy of Ligustrazine liposomes in the treatment of focal cerebral ischemic stroke of rats. Method: In this study, a rat model with focal cerebral ischemia was replicated by suture embolization. The efficacy of Ligustrazine liposomes was studied by testing neurological scores, brain index, cerebral infarction index, combined with anti-thrombotic experiments in rats and platelet aggregation inhibition experiments. Result: According to the experiment, Ligustrazine liposome can ease the neurological symptoms, and decrease the cerebral infarction index in model animals, and can slow down thrombosis, reduce the severity of thrombosis, and reduce the maximum platelet aggregation rate. To some extent, Ligustrazine liposomes has anti-cerebral ischemic stroke in rats. Conclusion: This experiment proved the therapeutic effect of ligustrazine liposomes on cerebral ischemic stroke in rats, and provided a theoretical basis for the clinical use of Ligustrazine liposomes for the treatment of ischemic stroke.

Predictive value of platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism.

The present study investigated the predictive value of the platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism. From January 2014 to January 2016, 23 patients with postpartum deep vein thrombosis of lower extremity treated in the Department of Obstetrics of Beijing Chaoyang Hospital were as assigned as the observation group. At the same time, 25 cases with normal recovery were assigned as the control group. Blood samples were collected from all the subjects. The platelet aggregation rate was measured using a platelet aggregation apparatus. Plasma platelet activating factor (PAF) levels were measured by ELISA. The positive rate of platelet P-selectin (CD62p) and lysosomal membrane glycoprotein (CD63) was measured by flow cytometry. PI3K expression and AKt phosphorylation levels were measured by western blot analysis. The ROC curve was used to evaluate the value of the platelet aggregation rate in predicting postpartum deep vein thrombosis of lower extremity. The correlation between the platelet aggregation rate and PAF and PI3K/AKt expression was also analyzed. The cesarean section rate, platelet 5-min maximum aggregation rate, PAF level and the positive rate of CD62p and CD63 were significantly higher in the control than those in the observation group (P<0.05). Furthermore, the platelet aggregation rate was positively correlated with the expression of PAF, CD62p and CD63 (r=0.389, 0.451, and 0.452; all P<0.05). The platelet 5-min maximum aggregation rate for predicting postpartum deep vein thrombosis of lower extremity was reflected by the area under the ROC curve (AUC=0.797, P=0.000). The PI3Kp110β/β-actin and p-AKt/AKt ratio was significantly higher in the observation compared with the control group (P<0.05). In addition, the platelet aggregation rate was positively correlated with the expression of PI3K and phosphorylation level of AKt (r=0.441, 0.430; all P<0.05). The results suggested that platelet aggregation activity is elevated in postpartum deep vein thrombosis patients. It has a certain predictive value for the occurrence of postpartum deep vein thrombosis of lower extremity. Thuss, the PI3K/AKt signaling pathway may be one of the mechanisms of platelet aggregation.

Antithrombotic effects of cilostazol combined with clopidogrel and aspirin in senile patients with cerebrovascular disease after PCI surgery

Objective To analyze the antithrombotic effects of cilostazol combined with aspirin and clopidogrel in elderly patients with cerebrovascular disease after PCI. Methods 100 elderly patients with cerebrovascular diseases who treated with coronary artery interventional therapy (PCI) were randomly divided into the control group and the observation group according to the digital table, 50casess in each group.The two groups were given control of blood pressure, blood lipids, blood sugar, improve circulation and other conventional treatment.The control group was treated with aspirin combined with clopidogrel, the observation group was treated with cilostazol based on the treatment of control group.Before and after treatment for 1, 4 and 8 weeks, the platelet aggregation degree was detected by PL-11 automatic platelet analyzer.During 2 months of follow-up, the degree of platelet aggregation, the volume of platelets, the efficacy of treatment and the incidence of adverse reactions were compared. Results The platelet aggregation rate between the two groups had no statistically significant difference before treatment (t0=2.782, P>0.05). After treatment, the platelet aggregation rate of the two groups decreased significantly, but after treatment for 1, 4 and 8 weeks, the platelet aggregation rates of the observation group were significantly lower than those of the control group [(51.87±9.65)%, (40.85±10.24)%, (38.52±9.64)%; (69.25±8.41)%, (62.43±9.22)%, (58.46±10.18)%], the differences were statistically significant (t1=5.693, t4=4.846, t8=6.719, all P 0.05). After treatment, the platelet volume of the two groups decreased significantly (t1=1.656, t4=1.438, t8=2.189, all P 0.05). The effective rate of the observation group was 94.00%(47/50), which was significantly higher than that of the control group [82.00%(41/50)], the difference was statistically significant (χ2=4.683, P<0.05). The incidence rates of adverse reactions in the observation group and the control group were 10.00% (5/50) and 8.00% (4/50), respectively, there was no statistically significant difference between the two groups (χ2=1.947, P=0.136). Conclusion Cilostazol combined with clopidogrel and aspirin in the treatment of elderly patients with cerebrovascular disease after PCI can significantly reduce platelet aggregation rate, improve clinical curative effect, and has certain clinical value. Key words: Cerebrovascular disorders; Angioplasty; Aspirin; Clopidogrel; Antithrombotic effect; Cilostazol

Effect of compatibility of ginkgolide A, ginkgolide B and ginkgolide K

To investigate the best active compatibility of ginkgolide A, B and K (GA，GB，GK). The effects of GA, GB, GK alone, combinations of each two of them, and combinations of these three components on platelet-activating factor (PAF)-induced platelet aggregation activity and rat cerebral ischemia reperfusion model (tMCAO) were compared in this study. Different compatibilities of GA, GB and GK could significantly reduce the maximum aggregation rate of PAF-induced platelet aggregation, and the effect was most obvious in combination of the three. Different compatibilities of GA, GB and GK could alleviate the neural function, cerebral infarction volume and cerebral edema in the tMCAO model of rats to different degrees, and the effect of combinations of the three was stronger than those of combinations of two and single use. The combination of all of GA, GB and GK had the strongest effect on nerve injury caused by anti-platelet aggregation in tMCAO rats.

Protection of Shuxuetong combined with aspirin against cerebral ischemia/reperfusion injury through ameliorating coagulation and fibrinolysis system

ObjectiveTo explore the influence of the combination of Shuxuetong (SXT) and aspirin on coagulation and fibrinolytic system of rats. MethodsSuture method was applied to establish focal cerebral ischemia-reperfusion injury models in rats. SD rats were randomly divided into sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, aspirin group, SXT group, and SXT + aspirin group (S&A). The neurological deficits were assessed according to Longa's grade 5 scoring method. The cerebral edema was detected by measuring the content of water in brain tissue. The volume of cerebral infarction was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Blood plasma was collected by abdominal aortic method to test maximum platelet aggregation rate and four blood coagulation. CD61, CD62p, 6-keto prostaglandin F1α (6-keto-PGF1α), antithrombin Ⅲ (AT-Ⅲ), D-dimer, plasminogen activator inhibitor-1 (PAI-1), tissue factor (TF), tissue plasminogen activator (t-PA), platelet thromboxane B2 (TXB2), and von Willebrand factor (vWF) content in rat plasma were detected by ELISA. ResultsSXT combined with aspirin could improve the neurological deficits, alleviate cerebral edema, and decrease the cerebral infarct value. Compared with the sham operation group, fibrinogen (FIB), 6-PGF1α, AT-III, and t-PA in model group were significantly decreased; Compared with the model group, the above-mentioned indexes in SXT and aspirin treatment group were significantly increased. The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer, PAI-1, TF, TXB2, and vWF of the model group were significantly increased; The above-mentioned indexes in blood SXT + aspirin treated group were significantly decreased. There was a significant difference between the combined group and SXT group. The maximum concentration of plateletsin aspirin treated rats was significantly decreased, however, MPAR was reversed in SXT + aspirin treated group. ConclusionSXT combined with aspirin can effectively inhibit platelet activation, regulate the maximum concentration of platelets, and improve coagulation function and fibrinolysis system.

Panax quinquefolius saponins combined with dual antiplatelet drug therapy alleviate gastric mucosal injury and thrombogenesis through the COX/PG pathway in a rat model of acute myocardial infarction.

ObjectivesPrevious studies have found that Panax quinquefolius saponins (PQS) combined with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel enhances antithrombotic effects while reducing gastric mucosal injury induced by DAPT. We investigated the effects of the combined drug therapy (PQS+DAPT) through the COX/PG pathways.MethodsAcute myocardial infarction (AMI) was induced in Wistar rats by ligation of the left anterior descending (LAD) coronary artery, and the animals were randomly divided into Model, DAPT, and PQS+DAPT groups. Rats in the sham group did not undergo artery ligation. They were intragastrically treated for 14 days. Myocardial infarct size; myocardial pathology; platelet aggregation rate, CD62p activation, concentrations of thromboxane B2 (TXB2), 6-keto-PGF1α, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI), the TXB2/6-keto-PGF1α ratio were measured. The ultrastructure of the gastric mucosa was observed by scanning electron microscopy. The expression of PGE2 and 6-keto-PGF1α in gastric mucosa was measured by radioimmunoassay, and levels of COX-1, COX-2, and VEGF in gastric mucosa were assessed using immunohistochemistry.ResultsThe addition of Panax quinquefolius saponins (PQS+DAPT) to standard DAPT therapy significantly decreased the myocardial infarct area, degree of myocardial lesions, TXB2 and PAI levels, and the TXB2/6-keto-PGF1α ratio, while increasing 6-keto-PGF1α and t-PA levels and reducing the degree of gastric mucosal injury. Expression of PGE2, 6-keto-PGF1α, COX-2, and VEGF in the gastric mucosa was upregulated in the PQS+DAPT group compared with the standard DAPT group.ConclusionPQS increases the degree of DAPT inhibition of myocardial necrosis and antiplatelet effects in AMI rats, as well as reducing damage to the gastric mucosa caused by DAPT. The mechanism may be related to inhibition of TXB2 and PAI activity and elevation of 6-keto-PGF1α and t-PA levels in blood, and may be associated with upregulated expression of COX-2, PGE2, PGI2, and VEGF in gastric tissue.

Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats.

2-Arachidonoylglycerol (2-AG) is a major modulator of blood flow and platelet aggregation and a potential neuroprotectant. The present study investigated, for the first time, the effects of 2-AG on cerebral blood flow (CBF) in the first critical hours during middle cerebral artery occlusion (MCAO) and on platelet aggregation in rats. Adult male Sprague-Dawley rats ( n = 30) underwent permanent MCAO under isoflurane anesthesia and were randomly assigned to receive either 2-AG (6 mg/kg iv), monoacylglycerol lipase inhibitor JZL-184 (10 mg/kg iv), or vehicle ( n = 6 rats/group) treatment. CBF and cardiovascular responses were measured, by a blinded investigator, for up to 4 h. In separate experiments, platelet aggregation by 2-AG (19-300 µM) was assessed by whole blood aggregometry ( n = 40). 2-AG and JZL-184 significantly increased the severity of the CBF deficit versus vehicle (20.2 ± 8.8% and 22.7 ± 6.4% vs. 56.4 ± 12.1% of pre-MCAO baseline, respectively, P < 0.05) but had no effect on blood pressure or heart rate. While JZL-184 significantly increased the number of thrombi after MCAO, this did not reach significance by 2-AG. 2-AG induced platelet aggregation in rat whole blood in a similar manner to arachidonic acid and was significantly reduced by the cyclooxygenase inhibitors indomethacin and flurbiprofen and the thromboxane receptor antagonist ICI 192,605 ( P < 0.05). This is the first study showing that 2-AG increases the severity of the CBF deficit during MCAO, and further interrogation confirmed 2-AG-induced platelet aggregation in rats. These findings are important because 2-AG had previously been shown to exert neuroprotective actions and therefore force us to reevaluate the circumstances under which 2-AG is beneficial. NEW & NOTEWORTHY 2-Arachidonoylglycerol (2-AG) has neuroprotective properties; however, the present study revealed that 2-AG increases the severity of the cerebral blood flow deficit during middle cerebral artery occlusion in rats. Further interrogation showed that 2-AG induces platelet aggregation in rats. These findings force us to reevaluate the circumstances under which 2-AG is beneficial.

Increased Thrombogenicity in Chronic Renal Failure in a Rat Model Induced by 5/6 Ablation/Infarction.

PurposeAbnormalities in hemostasis and coagulation have been suggested in chronic renal failure (CRF). In this study, we compared processes of thrombus formation between rats with CRF and those with normal kidney function.Materials and MethodsCRF was induced by 5/6 ablation/infarction of the kidneys in Sprague-Dawley rats, and surviving rats after 4 weeks were used. Ferric chloride (FeCl3)-induced thrombosis in the carotid artery was induced to assess thrombus formation. Whole blood clot formation was evaluated using rotational thromboelastometry (ROTEM). Platelet aggregation was assessed with impedance platelet aggregometry.ResultsFeCl3-induced thrombus formation was initiated faster in the CRF group than in the control group (13.2±1.1 sec vs. 17.8±1.0 sec, p=0.027). On histological examination, the maximal diameters of thrombi were larger in the CRF group than in the control group (394.2±201.1 µm vs. 114.0±145.1 µm, p=0.039). In extrinsic pathway ROTEM, the CRF group showed faster clot initiation (clotting time, 59.0±7.3 sec vs. 72.8±5.0 sec, p=0.032) and increased clot growth kinetics (α angle, 84.8±0.2° vs. 82.0±0.6°, p=0.008), compared to the control group. Maximal platelet aggregation rate was higher in the CRF group than in the control group (58.2±0.2% vs. 44.6±1.2%, p=0.006).ConclusionOur study demonstrated that thrombogenicity is increased in rats with CRF. An activated extrinsic coagulation pathway may play an important role in increasing thrombogenicity in CRF.

Changes of platelet rheological behavior and the interventional effects of ulinastatin in rats with high-voltage electrical burns

Changes of platelet rheological behavior and the interventional effects of ulinastatin in rats with high-voltage electrical burns

Levels of antithrombin III and D-dimers as predictors of pulmonary artery thromboembolism in patients with deep vein thrombosis

Aim. Search for predictors of pulmonary artery thromboembolism in patients with deep vein thrombosis among the indicators of hemostasis system. Methods. Retrospective analysis of indicators of hemostasis system was performed in 23 patients with defined pulmonary artery thromboembolism, 30 patients with deep vein thrombosis and 20 healthy volunteers. Values of platelet aggregation by Born method, concentration of circulating thrombocytic aggregates by Kohanna method, values of thromboelastometry, as well as blood levels of D-dimers and antitrombin III in arterial and venous blood were measured. Results. It was established that in patients from both thrombosis groups, haemostasis system changes are similar in nature: (1) a high value of Wu-Hoak is registered - more than 15 times higher in both arterial and venous blood compared to the control group; (2) platelet aggregation rates demonstrate hyperaggregation with all inductors, both in arterial and venous blood; (3) thromboelastography results are characterized by increased activity of thrombocytic hemostasis, prolonged clotting time, heightened clot strength compared to control in both arterial and venous blood flow. However, the difference was revealed between groups with and without pulmonary thromboembolism in venous blood levels of D-dimers and activity of antithrombin III. A function to predict pulmonary thromboembolism was constructed depending on the level of D-dimers and activity of antithrombin III in patients with deep vein thrombosis. Conclusion. The developed function for prediction of pulmonary artery thromboembolism can objectively assess the likelihood of pulmonary thromboembolism, which in turn allows minimizing risk and timely assessing the effectiveness of taken preventive measures.

Triterpenoids with antiplatelet aggregation activity from Ilex rotunda

Phytochemical studies on the barks of Ilex rotunda Thunb. had resulted in the isolation of seven previously undescribed triterpenoids, rotundinosides E-K, along with sixteen known ones. The structures of previously undescribed compounds were elucidated on the basis of extensive spectroscopic analysis and the sugar moieties were further identified by HPLC and GC after acid hydrolysis. Among the isolates, rotundinoside F featured a rare triterpene-phenylpropanoid hybrid structure and rotundinoside H was an uncommon triterpene saponin with α-linked glucopyranosyl moiety at C-3. The antiplatelet aggregation of all compounds were evaluated against ADP induced rat platelet aggregation in vitro, and five compounds exhibited moderate inhibitory effects with IC50 values ranging from 22.4 to 32.8 μM.