Acute Pulmonary Embolism Group Research Articles

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model.

Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

Discrimination of the acute pulmonary embolism subtypes based on the novel MAPH score.

Acute pulmonary embolism (APE) is a thromboembolism situation that can be central or peripheral. APE risk analysis and classification are essential for therapy planning. Our aim is to determine the novel MAPH score (including age, mean platelet volume (MPV), total protein, and hematocrit parameters) that can distinguish APE subtypes. Our retrospective cohort analysis includes 97 APE patients referred to the emergency medicine department who underwent pulmonary computed tomography angiography (CTA) in 24h from 2020 to 2022. The hospital information system provided demographic, clinical, laboratory, and pulmonary CTA data. APE was classified into central (46 patients) and peripheral (51 patients) depending on the area of vascular involvement. The central APE group had higher hypertension (HT) (67.4%) and atrial fibrillation (AF) (39.1%) incidence than the peripheral APE group (all p values > 0.05). The central APE had higher total protein and platelet counts (p = 0.003 and p = 0.036), but peripheral APE had higher troponin values (p = 0.029). Central APE had 2.17 ± 0.85 MAPH and peripheral APE 1.76 ± 0.95 (p = 0.029). HT, AF, platelet count, and MAPH score differed significantly in univariate logistic regression (all p values < 0.05). However, only platelet count varied in multivariate logistic regression (p = 0.042). ROC curve analysis revealed that the MAPH score predicts central APE with 83% sensitivity and 45% specificity at a cut-off level of 1.5. The new MAPH score as an indicator of blood viscosity may distinguish between central and peripheral APE. Our result is significant, especially for centers with limited examinations, as it may accelerate the diagnosis and treatment processes. We think that our results might guide future investigations.

Correlation Between Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with Risk Stratification Indicators and Thrombus Burden in Patients with Moderate-to-High Risk Acute Pulmonary Embolism, and Changes After Treatment.

To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.

Curcumin inhibits acute pulmonary embolism and inflammation by inhibiting high mobility group box 1 (HMGB1)

This study assessed the role of Curcumin in acute pulmonary embolism (APE) and inflammation. Male rats were assigned into sham operation group, APE group, low-dose and high-dose of Curcumin group for this study. Levels of IL-1β, TNF-α, and Interleukin-6 (IL-6) inflammatory indicators were analyzed, including also, pathological changes of lung tissue. We also assessed High mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE) and Nuclear factor kappa B (NF-κB) protein expressions. Results showed that, inflammation indicators were reduced after treatment at 6 h, 24 h, and 72 h, when compared with APE group, but were still higher than sham operation group (P &lt;0.05). Serum inflammation index was higher at 2 h after modeling (P &lt;0.05). Moreover, treatment groups showed continuously reduced HMGB1 protein expression, with lower level of HMGB1 in high dose group (P &lt;0.05). RAGE expression continued to increase in APE and treatment groups (P &lt;0.05). However, its level in treatment groups was lower than APE group (P &lt;0 05). The NF-KB expression continued to increase in APE and treatment groups (P &lt;0.05) with a lower level in treatment group (P &lt;0.05). Curcumin effectively suppressed inflammatory response in acute pulmonary embolism, by reducing RAGE/NF-KB signal activity and inhibiting inflammatory response by inhibiting HMGB1 expression.

Acil Serviste Pulmoner Tromboemboli Tanısı Konulan Hastalarda Hematolojik Parametrelerin Klinik Önemi

Objective: Acute pulmonary embolism (APE) is a highly fatal acute clinical condition. Herein, we aimed to determine the role of blood parameters in the diagnosis and prognostication of APE.&#x0D; Material and Method: This study was conducted retrospectively on patients who had been admitted to our hospital’s emergency department (ED) and diagnosed with APE. Patients with an RV/LV ratio greater than 0,9 on Computed tomography (CT) and hypotension were grouped as massive APE; patients with stable hemodynamics and an RV/LV ratio greater than 0,9 on CT were defined as submissive APE; and patients with stable hemodynamics and an RV/LV ratio smaller than 0,9 on CT were defined as non-massive APE.&#x0D; Results: This study enrolled a total of 200 patients, 82 of which were male (41%) and 118 were female (59%). APE group had a significantly greater D-dimer level than the control group (3.559,5±8.611.3 ng/ml vs 266.6±266.6 ng/ml) (p

Index of cardiac-electrophysiological balance and the effects of thrombolytic therapy on the electrocardiogram of patients with pulmonary embolism.

Different parameters on electrocardiograms (ECG) have been investigated to predict arrhythmia and mortality in patients with acute pulmonary embolism (APE). The acute effect of thrombolytic therapy (TT) on these parameters has not been investigated yet. We examined the data of 83 patients who were evaluated as high-risk APE and discharged from the hospital after TT. First, the high-risk APE patients' ECGs were compared with healthy control subjects (n = 55). After their admission and 24 hours later, the ECGs of patients with APE were compared. Heart rate, P-wave morphology, QRS duration, QT distance, Tp-e, and the index of cardiac electrophysiological balance (iCEB) were analyzed. Although P maximum was not different between the groups' ECGs, heart rate, QT, QTc (corrected QT) interval, Tp-e intervals, Tp-e/QT ratio, and P wave dispersion were significantly higher in the APE group ( P values < 0.031). iCEB or iCEBc (corrected iCEB) values were lower in APE group ( P < 0.001). After TT, we determined a decrease in heart rate, Tp-e interval, and Tp-e/QT ratio ( P < 0.001). Although we detected a decrease in the QT and QTc interval and QT dispersion (QTd), QTd had no statistical significance (respectively P -value 0.013, 0.029, and 0.096). The iCEB and iCEBc levels were lower after TT ( P -value was 0.035 and 0.044 respectively). The QT, QTc, Tp-e interval, Tp-e/QTc ratio, iCEB, and iCEBc values significantly decreased after TT. It may be thought that effective TT causes partial improvement in ventricular repolarization in an early period.

The Predictive Value of microRNA-134 and microRNA-1233 for the Early Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Pulmonary Embolism.

BackgroundThe differential diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with acute pulmonary embolism (APE) complications are difficult because of the variability of clinical presentations and the shortage of an unfailing screening biomarkers or instruments.ObjectiveAimed to detect and compare the expression of serum microRNAs (miR-1233, miR-134) in AECOPD patients complicated with APE.Patients/MethodsBlood samples were collected from 52 AECOPD patients (13 patients with APE complications, 39 patients without APE) and 10 patients with stable COPD. Serum miRNAs expression was detected with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The levels of plasma D-dimers were determined by detection with an enzyme-linked immunosorbent assay (ELISA). The receiver-operator characteristic (ROC) curve was used for evaluating the diagnostic accuracy of the studied miRNAs.ResultsAccording to the Wells score, 42 of the 52 AECOPD patients were unlikely to have APE (≤4 points), whereas the remaining 10 (>4 points) were likely to have APE. There were 4 cases (4/13 30.8%) in the AECOPD combined with APE group with a Wells score of >4 points. The expression levels of miR-1233 and miR-134 in the serum were considerably upregulated in the AECOPD+APE group compared with the AECOPD group and the stable COPD group (P<0.05). The areas under the curve (AUCs) for miR-134 and miR-1233 were, respectively, 0.931 (95% CI 0.863–0.999) (P<0.05) and 0.884 (95% CI 0.79–0.978) (P<0.05) and were higher compared with the AUC for D-dimer of 0.628 (95% CI 0.447–0.809), the AUC for age-adjusted D-dimer of 0.705 (95% CI 0.525–0.885) and the AUC for Wells score of 0.577 (95% CI 0.389–0.765).ConclusionOur study indicated that serum miR-1233 and miR-134 have high clinical value in the early diagnosis of AECOPD patients combined with APE, or could be used as potential biomarkers for clinical identification of AECOPD with or without APE complication.

Predictive value of the Wells score combined with D-dimer level in identifying acute pulmonary embolism in patients with coronary heart disease with chest pain.

Predictive value of the Wells score combined with D-dimer level in identifying acute pulmonary embolism in patients with coronary heart disease with chest pain.

Plasma fibrin clot proteomics in patients with acute pulmonary embolism: Association with clot properties

It has been reported that 476 proteins can be detected in plasma fibrin clots from patients with venous thromboembolism. Plasma fibrin clots proteomic composition in relation to their properties has not been studied in acute pulmonary embolism (PE). Clots generated from plasma of 20 PE patients and 20 healthy controls were assessed using mass spectrometry, clot permeability (Ks), and clot lysis time (CLT). The proteomic composition of plasma fibrin clots from acute PE patients differed from that of control subjects in regard to 198 clot-bound proteins. In the acute PE group, we observed increased clot-bound fibrinogen, apolipoprotein B-100, platelet glycoprotein Ib, lipopolysaccharide-binding protein, and histones H3 + 4 and reduced fibronectin, α2-antiplasmin, α2-macroglobulin, factor (F)XIII, histidine-rich glycoprotein, antithrombin, von Willebrand Factor, plasminogen, and prothrombin. Among PE patients, low Ks (≤3.83 × 10−9 cm2) was associated with increased clot-bound C-reactive protein, kininogen-1, protein S, β-2-microglobulin, and thromboxane-A synthase when compared with patients having Ks > 3.83 × 10−9 cm2. Ks correlated inversely with FIX and FV, thrombin-activatable fibrinolysis inhibitor, complement C1s, C7, C8, and apolipoprotein A-I. The specific protein composition in plasma fibrin clots from acute PE patients is associated with denser clot formation. Several proteins unrelated to the coagulation system can modulate fibrin phenotype in acute thrombotic states. SignificanceOur study significantly advances the field of thrombosis and hemostasis. The plasma fibrin clot proteomics findings fill the gap of knowledge about the presence and the role of other proteins to the plasma fibrin clot in the acute phase of pulmonary embolism, aside fibrinogen, which is the main component of fibrin. The reported methodology, which involves the sample preparation using Multienzyme Digestion-Filter Aided Sample Preparation (MED FASP), data acquisition with the Quadrupole-Orbitrap mass spectrometer, and data analysis using the advanced tools such as MaxQuant, Total Protein Approach and Perseus, allows to gain not only the qualitative, but also the quantitative insights into the microworld of proteins entangled among the fibrin network. By comparing the clots formed from plasma of patients with acute pulmonary embolism with the clots from healthy control, we provide the specific protein composition associated with unfavorable clot properties observed in this disease. Moreover, our findings emphasize that several proteins unrelated to the coagulation system, can modulate fibrin phenotype in acute thrombotic states.

Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department.

ObjectivesTo evaluate the prevalence of acute pulmonary embolism (APE) in non-hospitalized COVID-19 patients referred to CT pulmonary angiography (CTPA) by the emergency department.MethodsFrom March 14 to April 6, 2020, 72 non-hospitalized patients referred by the emergency department to CTPA for COVID-19 pneumonia were retrospectively identified. Relevant clinical and laboratory data and CT scan findings were collected for each patient. CTPA scans were reviewed by two radiologists to determinate the presence or absence of APE. Clinical classification, lung involvement of COVID-19 pneumonia, and CT total severity score were compared between APE group and non-APE group.ResultsAPE was identified in 13 (18%) CTPA scans. The mean age and D-dimer of patients from the APE group were higher in comparison with those from the non-APE group (74.4 vs. 59.6 years, p = 0.008, and 7.29 vs. 3.29 μg/ml, p = 0.011). There was no significant difference between APE and non-APE groups concerning clinical type, COVID-19 pneumonia lung lesions (ground-glass opacity: 85% vs. 97%; consolidation: 69% vs. 68%; crazy paving: 38% vs. 37%; linear reticulation: 69% vs. 78%), CT severity score (6.3 vs. 7.1, p = 0.365), quality of CTPA (1.8 vs. 2.0, p = 0.518), and pleural effusion (38% vs. 19%, p = 0.146).ConclusionsNon-hospitalized patients with COVID-19 pneumonia referred to CT scan by the emergency departments are at risk of APE. The presence of APE was not limited to severe or critical clinical type of COVID-19 pneumonia.Key Points • Acute pulmonary embolism was found in 18% of non-hospitalized COVID-19 patients referred by the emergency department to CTPA. Two (15%) patients had main, four (30%) lobar, and seven (55%) segmental acute pulmonary embolism. • Five of 13 (38%) patients with acute pulmonary embolism had a moderate clinical type. • Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism.

Applications of computed tomography and ischemic modified albumin and D-D Levels in disease assessment of patients with acute pulmonary embolism

Objective To investigate the clinical application values of computed tomography (CT), ischemic modified albumin (IMA) and D-dimer (D-D) levels in the disease assessment of patients with acute pulmonary embolism (APE). Methods From June 2015 to June 2018, 100 suspected APE patients in our hospital were selected as the study subjects, after the CT gold inspection, the 80 patients diagnosed with APE were as APE group, including 38 cases in high-risk group and 42 cases in low-risk group: 20 non APE cases and 60 healthy volunteers at the same time were selected as control group. The serum IMA level was detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the plasma D-D level was detected by immunoturbidimetry. Receiver operating characteristc (ROC) curve was used to analyze the diagnostic values of IMA and D-D for APE disease. Results The levels of IMA and D-D in APE group were significantly higher than those in non APE group and control group (P<0.05); the levels of IMA and D-D in non APE group were significantly higher than those in control group (P<0.05), while those in high-risk group were significantly higher than those in low-risk group (P<0.05); CT examination after admission was as the gold standard for diagnosing APE disease; ROC curve showed that, the area under curve (AUC) of D-D and IMA in diagnosing APE was 0.875 and 0.763, respectively, with corresponding sensitivity 90.01% and 93.87%, specificity 52.21% and 95.65% respectively; the AUC of IMA combined D-D level in diagnosing APE was 0.834, the sensitivity was 95.87%, and the specificity was 78.69%; the AUC of D-D and IMA in diagnosing high-risk APE was 0.950 and 0.914, respectively, with the corresponding sensitivity 97.21% and 93.98%, specificity 31.58% and 76.98%, respectively. The AUC of IMA combined D-D level in diagnosing high-risk APE was 0.958, with sensitivity 96.39%, specificity 76.87%. Compared with CT results, in the 80 patients diagnosed with APE, there were 4 patients with negative IMA and 6 patients with negative D-D, and the control group samples test showed negative IMA and D-D levels were all negative. The consistency of CT combine with D-D ( Kappa=0.734, P=0.000), and CT combine with IMA (Kappa=0.819, P=0.000) were good. Conclusions According to the results of CT examination, IMA combined with D-D level has a good sensitivity and specificity in the diagnosis of APE, which can effectively improve the diagnostic rate of APE diseases, and provide an important basis for clinical rapid and reliable detection and treatment of APE diseases. Key words: Pulmonary embolism; Tomography, X-ray computed; Serum albumin; Fibrin fibrinogen degradation products

Comparison between Negative T waves characteristics in acute coronary syndrome and pulmonary embolism

BackgroundElectrocardiogram (ECG) is the first available modality used in patients with chest pain and dyspnea in emergency rooms.We aimed to study differences between acute coronary syndrome (ACS) and acute pulmonary embolism (APE) in patients presented primarily with abnormal negative T waves on their admission Electrocardiogram. MethodsThis research was a retrospective study in which 297 patients (97 patients with APE and 200 with ACS) were included. The patients were admitted to the emergency ward of a tertiary heart center between 2015 and 2017. In addition to the evaluation of distribution of negative T waves, the depth of the inverted precordial T waves was measured. ResultsThe mean age of patients was 62.0 ± 11.4 in ACS group and 60.7 ± 17.6 in APE group (P value = 0.563). Total negative T in V3 and V4 in ACS and APE groups was 9.1 mm and 4.2 mm respectively (P value <0.001).Total magnitude of negative T in anterior leads divided by total magnitude of negative T in inferior leads for ACS and APE groups were 15.1 ± 12.0 and 5.4 ± 3.6 respectively (P value = 0.001).ROC curves showed that total magnitude of negative T in V4 divided by negative T in V1 can be valuable. A cutoff point of 1.75 with sensitivity of 73.5% and specificity of 84.9% (95% CI 0.79–0.91 P < 0.001) could differentiate APE patients from ACS patients. ConclusionThis study suggests that total magnitude of negative T in left precordial leads divided by right precordial leads can be valuable in differentiating APE from ACS.

The diagnostic role of N-terminal brain natriuretic peptide in identifying acute pulmonary thromboembolism versus congestive heart failure in dyspnea patients

Objective To explore the role of NT-proBNP in the differentiation of acute pulmonary embolism (APE) from congestive heart failure (CHF) in patients with acute dyspnea. Methods Consecutive 260 patients aged ≥ 60 years complaining of acute dyspnea were collected between June 2010 and October 2015.The patients were divided into two groups of APE and CHF according to their diagnosis standards.The levels of NT-proBNP between the two groups were compared using t-test, and receiver operating characteristic curve (ROC curve) was made to show the value of NT-proBNP in differentiation of APE from CHF. Results Patients in APE group had significantly lower median levels of NT-proBNP as compared with patients in CHF group [(2 478.8±1 473.9)ng/L vs.(5 955.4±3 180.1)ng/L, t=-12.020, P<0.01]. The ROC curve of APE existence against serum levels of NT-proBNP showed an optimal cut-point of NT-proBNP of 1 518 ng/L, with specificity up to 98.8%, and the area under the ROC curve for NT-proBNP was 0.877. Conclusions NT-proBNP as a simple and bedside approach to identify APE versus CHF patients with acute dyspnea can help clinicians identify APE early and reduce the rates of misdiagnosis and missed diagnosis of APE.But the confirmative diagnosis of APE is still based on spiral CT angiography. Key words: Pulmonary embolism; Heart failure; Natriuretic peptide, brain

Serum copeptin level may not play an important role in acute pulmonary embolism

Objective: To evaluate serum copeptin levels in acute pulmonary embolism (APE) patients and healthy controls and to determine the role of the serum copeptin level in the diagnosis and severity of APE. Methods: This prospective, case-control study was conducted in the Department of Chest Diseases. Fifty patients newly diagnosed with pulmonary embolism and 39 healthy individuals were enrolled. The diagnosis of APE was confirmed by computed tomography angiography. Copeptin levels were evaluated in both groups. All APE patients were evaluated with echocardiography to identify right ventricular dysfunction and to measure the pulmonary artery systolic pressure (PASP). Patients with APE were classified according to the risk of early mortality. The correlation between early mortality risk and PASP and copeptin levels was evaluated in patients with APE. Results: There was no significant difference between the APE and control groups in age or gender (both, p>0.05), and serum copeptin levels were similar between the two groups (p=0.309). The relationship between serum copeptin levels and early mortality risk and PASP in the APE group was also evaluated. There was no correlation between early mortality risk and serum copeptin levels and PASP. Conclusion: The serum copeptin level, which is an important prognostic marker for cardiovascular diseases, may not be a suitable biomarker for APE.

Effect of simvastatin on the SIRT2/NF-κB pathway in rats with acute pulmonary embolism

Context: Statins have been widely used in acute pulmonary embolism (APE), while simvastatin has been well-established for the prevention of pulmonary hypertension, which was supposed to be an attractive recommendation for APE treatment.Objective: The current article studies the effect of simvastatin on the SIRT2/NF-κB pathway in rats with APE.Materials and methods: Sprague-Dawley rats were divided into four groups (n = 24 per group): control group, rats were treated with saline once daily for 14 days before administration of saline (sham group) or a suspension of autologous emboli (APE group), or rats were treated with simvastatin (10 mg/kg) for 14 days before administration of autologous emboli (APE + simvastatin) group. The RVSP, mPAP and the arterial blood gas was analyzed. Besides, plasma inflammatory cytokines and MMPs levels, as well as the expression of SIRT2/NF-κB pathway were determined.Results: Compared with the control and sham groups, the levels of mPAP (31.06 ± 3.47 mmHg), RVSP (35.12 ± 6.02 mmHg), A-aDO2 (33.14 ± 6.16 mmHg) and MMP-9 (6.89 ± 0.84 ng/mL) activity were significantly elevated, but PaO2 (66.87 ± 7.85 mmHg) was highly decreased in rats from APE group at 24 h after APE. Meanwhile, the inflammatory changes were aggravated by the enhanced levels of TNF-α (138.85 ± 22.69 pg/mL), IL-1β (128.47 ± 22.14 pg/mL), IL-6 (103.16 ± 13.58 pg/mL) and IL-8 (179.28 ± 25.79 pg/mL), as well as increased NF-κB (5.29 ± 0.47 fold), but reduced SIRT2 (59 ± 6% reduction), and eNOS (61 ± 5% reduction) mRNA in APE rats. APE rats treated with simvastatin led to a significant opposite trend of the above indexes.Conclusions: Simvastatin protects against APE-induced pulmonary artery pressure, hypoxemia and inflammatory changes probably due to the regulation of SIRT2/NF-κB signalling pathway, which suggest that simvastatin may have promising protective effects in patients with APE.

The effects of low-molecular-weight heparin on lung and pulmonary artery injuries in acute pulmonary embolism rat model via platelet-derived growth factor-β

ObjectiveTo evaluate the effects of anticoagulant agent (low-molecular-weight heparin, LMWH) on the pulmonary artery intima hyperplasia of rats with acute pulmonary embolism (APE) by assaying platelet-derived growth factor-β (PDGF-β). MethodsA total of 90 Sprague-Dawley rats were randomly assigned into the sham, APE, and LMWH groups with 30 rats in each group. The APE rat models were established by injecting autologous blood clots via external jugular veins. In each group, six mice were sacrificed at the 1st day (D1), 4th day (D4), 7th day (D7), 14th day (D14), and 28th (D28) subsequent to the induction of APE to collect the lungs. Right ventricle pressure (RVP) and mean pulmonary arterial pressure (mPAP) were measured. Western blot and RT-PCR analyses were used to assess PDGF-β expression at various time points. In addition, changes in lung pathology were evaluated using hematoxylin and eosin (H&E) staining and electron microscope. ResultsThe overall success rate of establishing APE rat models was 85.7% (60/70). There was no difference in mPAP between the sham group and the APE group at the D1, D4, D7, and D14. However, at the D28, mPAP in the APE group was significantly higher than that in the sham group. There was no difference among the three groups regarding RVP. PDGF-β expression were decreased in the LMWH group at all time points compared with the sham and APE groups (P<0.01). Furthermore, pulmonary embolism, alveolar wall necrosis and hemorrhage, and inflammation were significantly attenuated in the LMWH group compared with the sham and APE groups subsequent to the induction of APE. ConclusionLMWH attenuates lung and pulmonary artery injuries and improves prognosis. Decreased PDGF-β in the lungs may be the important factor in the effects observed.

The prognostic importance of thiol/disulfide homeostasis in patients with acute pulmonary thromboembolism

ObjectiveThe aim of this study was to evaluate the role of thiol/disulfide homeostasis in acute pulmonary embolism (APE) and investigate its compliance to show hospital mortality of patients with APE. Material and MethodsA total of 173 participants including 113 patients with APE, and 60 healthy individuals were included in the study. APE group was categorized into two subgroups according to Pulmonary Embolism Severity Index (PESI) clinic risk score (PESI low group [n=71, class 1-3] and PESI high group [n=42, class 4-5]). ResultsMean level of native thiol was lower and disulfide level and disulfide/total thiol ratio were higher in APE group than control group. In APE group, 14 patients died during hospitalization. Native thiol and disulfide level, presence of shock, heart rate, oxygen saturation, right ventricular dysfunction, N-terminal pro–brain natriuretic peptide, and creatinine levels were found to have prognostic significance in univariate analysis. On multilvariable logistic regression analysis, native thiol and disulfide level (odds ratio [OR], 1.16(0.87-1.36); P=.010 and OR, 1.49; P=.015, respectively), presence of shock (OR, 1.04; P=.012) and N-terminal pro–brain natriuretic peptide (OR, 1.67; P=.002) were strong predictors for APE-related hospital mortality after the adjustment of other potential confounders. ConclusionWe have shown that thiol/disulfide homeostasis can be altered during APE and associated with worse hemodynamic parameters, and may be used as a prognostic marker for hospital mortality.

The diagnostic value of serum copeptin levels in an acute pulmonary embolism.

Acute pulmonary embolism (APE) is a common disease which is associated with high mortality and morbidity. Circulating level of copeptin, which was demonstrated to be elevated in heart failure, acute myocardial infarction and pulmonary arterial hypertension, were reported to be independent predictors of poor outcome in recent studies. The aim of the present study was to investigate the clinical utility of copeptin in the diagnosis of APE. A total of 90 consecutive patients, admitted to emergency service due to acute chest pain and/or dyspnea and who underwent pulmonary computerized tomography angiography (CTA) due to suspicion of APE, were included in this prospective study. The patients diagnosed with APE were defined as APE (+) group and the remaining individuals with normal pulmonary CTA result were defined as APE (-) group. Copeptin levels (7.76 ± 4.4 vs. 3.81 ± 1.34 ng/dL; p < 0.001) were higher in the APE (+) group as compared to the APE (-) group. Copeptin was significantly positively correlated with B-type natriuretic peptide (r = 0.434, p < 0.001), D-dimer (r = 0.315, p = 0.003) and troponin I (r = 0.300, p = 0.004) and inversely correlated with arterial oxygen saturations (r = -0.533, p < 0001). When the correlation of copeptin with right ventricular dysfunction parameters was investigated, it was significantly inversely correlated with the tricuspid annular plane systolic excursion (r = -0.521, p < 0.001) and positively correlated with right to left ventricle ratio (r = 0.329, p = 0.024). Copeptin (OR 1.836, 95% CI 1.171-2.878, p = 0.008) was found as a significant independent predictor of APE in a multivariate analysis, after adjusting for other risk parameters. Copeptin is a promising new biomarker, which may be used to support the need for further investigations and to improve the diagnosis of patients with APE.

D-dimer testing for safe exclusion and risk stratification in patients with acute pulmonary embolism in primary care.

Background:Safe exclusion and risk stratification are currently recommended for the initial management of patients with acute pulmonary embolism (APE). The aim of this study was to assess the safe exclusion and risk stratification value of D-dimer (DD) for APE when tested at the beginning of admission.Materials and Methods:All consecutive Chinese APE patients and controls were recruited from January 2010 to December 2012. All measurements of serum indexes were made in duplicate and blinded to the patients’ status. All the 40 patients with the first episode of APE were confirmed by multi-detector computed tomographic pulmonary angiography. The plasma prothrombin time (PT), activated partial thromboplastin time, thrombin time, fibrinogen, and DD levels were measured within 24 h of admission. We used the Mann-Whitney U-test to determine the differences between groups and drew receiver operator characteristic curve to evaluate the indexes’ value in the APE screening.Results:The PT and DD in the APE group were significantly higher than those in the disease control group (P < 0.05). Taking PT and DD as the useful screening tests for APE and AUC was 0.765 and 0.822, respectively. DD yielded the higher screening efficiency, with DD >1820 μg/L as cut-off value, the sensitivity, specificity, positive and negative predictive value was 82.5%, 75.2%, 56.9%, and 91.6%, respectively.Conclusion:The patients with APE showed significant higher DD levels compared with disease controls, suggesting a negative qualitative DD test result can safely and efficiently exclude APE in primary care.

The value of isovolumic acceleration for the assessment of right ventricular function in acute pulmonary embolism

AimThe aim of this study was to assess the value of tricuspid annulus myocardial isovolumic acceleration (IVA) in the assessment of right ventricular function in patients with acute pulmonary embolism (PE). MethodsFifteen patients (mean age 60.6±11.3 years) with acute PE were enrolled and a control group was formed of 15 patients with a similar mean age (60.3±11.5). Patients who were diagnosed with acute PE by thoracic computed tomography angiography underwent transthoracic echocardiography at the time of diagnosis and at one month after diagnosis. ResultsIn the control group IVA was 2.8±0.2 m/s2, while in the acute PE group, it was 2.0±0.1 m/s2 at the time of diagnosis and 2.9±0.1 m/s2 at the end of the first month. When IVA values of acute PE patients at the end of the first month were compared with their initial values and those of the control group, they had normalized (control and acute PE p<0.0001; control and PE at one-month follow-up p=0.983). ConclusionIn our study, IVA was shown to be a reliable marker of right ventricular systolic function in patients with acute PE.