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1.
J Magn Reson Imaging ; 59(1): 164-176, 2024 01.
Article in English | MEDLINE | ID: mdl-37013673

ABSTRACT

BACKGROUND: Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients. PURPOSE: To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values. STUDY TYPE: Retrospective cohort. POPULATION: Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM). FIELD STRENGTH/SEQUENCE: 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences. ASSESSMENT: Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months. STATISTICAL TESTS: Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%). RESULTS: ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM. CONCLUSIONS: T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: 5.


Subject(s)
Cardiomyopathies , Cardiomyopathy, Dilated , Diabetes Mellitus, Type 2 , Ventricular Dysfunction, Left , Humans , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/diagnostic imaging , Prognosis , Retrospective Studies , Diabetes Mellitus, Type 2/complications , Contrast Media , Glycated Hemoglobin , Magnetic Resonance Imaging, Cine/methods , Gadolinium , Ventricular Function, Left , Fibrosis , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/diagnostic imaging , Ischemia
2.
BMJ Open ; 13(6): e067469, 2023 06 07.
Article in English | MEDLINE | ID: mdl-37286325

ABSTRACT

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.


Subject(s)
Acute Aortic Syndrome , Aortic Dissection , Humans , Prospective Studies , Aortic Dissection/diagnosis , Aortic Dissection/surgery , Biomarkers , China/epidemiology , Observational Studies as Topic , Multicenter Studies as Topic
3.
J Geriatr Cardiol ; 19(10): 734-742, 2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36338280

ABSTRACT

BACKGROUND: Postoperative acute kidney injury (AKI) is a major complication associated with increased morbidity and mortality after surgery for acute type A aortic dissection (AAAD). To the best of our knowledge, risk prediction models for AKI following AAAD surgery have not been reported. The goal of the present study was to develop a prediction model to predict severe AKI after AAAD surgery. METHODS: A total of 485 patients who underwent AAAD surgery were enrolled and randomly divided into the training cohort (70%) and the validation cohort (30%). Severe AKI was defined as AKI stage III following the Kidney Disease: Improving Global Outcomes criteria. Preoperative variables, intraoperative variables and postoperative data were collected for analysis. Multivariable logistic regression analysis was performed to select predictors and develop a nomogram in the study cohort. The final prediction model was validated using the bootstrapping techniques and in the validation cohort. RESULTS: The incidence of severe AKI was 23.0% (n = 78), and 14.7% (n = 50) of patients needed renal replacement treatment. The hospital mortality rate was 8.3% (n = 28), while for AKI patients, the mortality rate was 13.1%, which increased to 20.5% for severe AKI patients. Univariate and multivariate analyses showed that age, cardiopulmonary bypass time, serum creatinine, and D-dimer were key predictors for severe AKI following AAAD surgery. The logistic regression model incorporated these predictors to develop a nomogram for predicting severe AKI after AAAD surgery. The nomogram showed optimal discrimination ability, with an area under the curve of 0.716 in the training cohort and 0.739 in the validation cohort. Calibration curve analysis demonstrated good correlations in both the training cohort and the validation cohort. CONCLUSIONS: We developed a prognostic model including age, cardiopulmonary bypass time, serum creatinine, and D-dimer to predict severe AKI after AAAD surgery. The prognostic model demonstrated an effective predictive capability for severe AKI, which may help improve risk stratification for poor in-hospital outcomes after AAAD surgery.

4.
Front Cardiovasc Med ; 9: 892696, 2022.
Article in English | MEDLINE | ID: mdl-35898275

ABSTRACT

Background: Massive bleeding throughout aortic repair in acute type A aortic dissection (ATAAD) patients is a common but severe condition that can cause multiple serious clinical problems. Here, we report our findings regarding risk factors, short-term outcomes, and predicting model for massive bleeding in ATAAD patients who underwent emergent aortic repair. Methods: A universal definition of perioperative bleeding (UDPB) class 3 and 4 were used to define massive bleeding and comprehensively evaluate patients. A total of 402 consecutive patients were enrolled in this retrospective study during 2019. Surgical strategies used to perform aortic arch procedures included total arch and hemiarch replacements. In each criterion, patients with massive bleeding were compared with remaining patients. Multivariable regression analyses were used to identify independent risk factors for massive bleeding. Logistic regression was used to build the model, and the model was evaluated with its discrimination and calibration. Results: Independent risk factors for massive bleeding included male sex (OR = 6.493, P < 0.001), elder patients (OR = 1.029, P = 0.05), low body mass index (BMI) (OR = 0.879, P = 0.003), emergent surgery (OR = 3.112, P = 0.016), prolonged cardiopulmonary bypass time (OR = 1.012, P = 0.002), lower hemoglobin levels (OR = 0.976, P = 0.002), increased D-dimer levels (OR = 1.000, P = 0.037), increased fibrin degradation products (OR = 1.019, P = 0.008), hemiarch replacement (OR = 5.045, P = 0.037), total arch replacement (OR = 14.405, P = 0.004). The early-stage mortality was higher in massive bleeding group (15.9 vs. 3.9%, P = 0.001). The predicting model showed a well discrimination (AUC = 0.817) and calibration (χ2 = 5.281, P = 0.727 > 0.05). Conclusion: Massive bleeding in ATAAD patients who underwent emergent aortic repair is highly associated with gender, emergent surgery, increased D-dimer levels, longer CPB time, anemia, and use of a complex surgical strategy. Since massive bleeding may lead to worse outcomes, surgeons should choose suitable surgical strategies in patients who are at a high risk of massive bleeding.

5.
Heart Lung Circ ; 31(1): 136-143, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34120843

ABSTRACT

AIM: To evaluate the effect of packed red blood cells (pRBCs), fresh frozen plasma (FFP), and platelet concentrate (PC) transfusions on acute kidney injury (AKI) in patients with acute Stanford type A aortic dissection (ATAAD) with total arch replacement (TAR). METHOD: From December 2015 to October 2017, 421 consecutive patients with ATAAD undergoing TAR were included in the study. The clinical data of the patients and the amount of pRBCs, FFP, and PC were collected. Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Logistic regression was used to identify whether pRBCs, FFP, and platelet transfusions were risk factors for KDIGO AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT). RESULTS: The mean ± standard deviation age of the patients was 47.67±10.82 years; 77.7% were men; and the median time from aortic dissection onset to operation was 1 day (range, 0-2 days). The median transfusion amount was 8 units (range, 4-14 units) for pRBCs, 400 mL (range, 0-800 mL) for FFP, and no units (range, 0-2 units) for PC. Forty-one (41; 9.7%) patients did not receive any blood products. The rates of pRBC, PC, and FFP transfusions were 86.9%, 49.2%, and 72.9%, respectively. The incidence of AKI was 54.2%. Considering AKI as the endpoint, multivariate logistic regression showed that pRBCs (odds ratio [OR], 1.11; p<0.001) and PC transfusions (OR, 1.28; p=0.007) were independent risk factors. Considering KDIGO stage 3 AKI as the endpoint, multivariate logistic regression showed that pRBC transfusion (OR, 1.15; p<0.001), PC transfusion (OR, 1.28; p<0.001), a duration of cardiopulmonary bypass (CPB) ≥293 minutes (OR, 2.95; p=0.04), and a creatinine clearance rate of ≤85 mL/minute (OR, 2.12; p=0.01) were independent risk factors. Considering RRT as the endpoint, multivariate logistic regression showed that pRBC transfusion (OR, 1.12; p<0.001), PC transfusion (OR, 1.33; p=0.001), a duration of CPB ≥293 minutes (OR, 3.79; p=0.02), and a creatinine clearance rate of ≤85 mL/minute (OR, 3.34; p<0.001) were independent risk factors. CONCLUSIONS: Kidney Disease: Improving Global Outcomes-defined stage AKI was common after TAR for ATAAD. Transfusions of pRBCs and PC increased the incidence of AKI, stage 3 AKI, and RRT. Fresh frozen plasma transfusion was not a risk factor for AKI.


Subject(s)
Acute Kidney Injury , Aortic Dissection , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Adult , Aortic Dissection/surgery , Aorta, Thoracic/surgery , Erythrocyte Transfusion , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
7.
J Card Surg ; 36(5): 1659-1664, 2021 May.
Article in English | MEDLINE | ID: mdl-32939857

ABSTRACT

OBJECTIVES: We seek to report our management protocol and early outcomes of acute type A aortic dissection (ATAAD) repair during the early phase of coronavirus disease 2019 (COVID-19). METHODS: From January 23 to April 30, 2020, we performed ATAAD repair for 33 patients, including three with pregnancy-related TAADs. Confirmation of COVID-19 depended on the results of two nucleic acid tests and pulmonary computed tomography scan. Based on testing results and hemodynamic stability, patients were triaged to an isolated intensive care unit or negative pressure operating room for emergency surgery. RESULTS: Mean age 50.2 ± 13.3 years and 20 were male (60.1%) and 8 patients were febrile (>37.3°C; 24.2%) and 17 were lymphopenic (51.5%). No patient was excluded from COVID-19 infection preoperatively. Extensive aortic repair with total arch replacement (TAR) was performed in 24 (72.7%), and limited proximal repair in 9 patients (27.3%). Cardiopulmonary bypass and cross-clamp times averaged 177 ± 34 and 88 ± 20 min for TAR, and 150 ± 30 and 83 ± 18 min for hemiarch, respectively. The mean operation time was 410 ± 68.3 min. Operative mortality was 6.1% (2/33). Complications included reintubation in four (12.1%), acute kidney failure in two (6.1%), and cerebral infarction in one (3.0%). No paraplegia nor re-exploration for bleeding occurred. COVID-19 was excluded in 100% eventually. No nosocomial infection occurred. Nor did any patient/surgical staff develop fever or test positive during the study period. CONCLUSIONS: The results of this study show that our management protocol based on testing results and hemodynamic stability in patients with ATAAD during the COVID-19 pandemic was effective and achieved favorable early surgical outcomes.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , COVID-19 , Acute Disease , Adult , Aortic Dissection/epidemiology , Aortic Dissection/surgery , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/epidemiology , Aortic Aneurysm, Thoracic/surgery , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , Time Factors , Treatment Outcome
8.
Biomed Res Int ; 2020: 7806409, 2020.
Article in English | MEDLINE | ID: mdl-32766314

ABSTRACT

Acute aortic dissection (AAD) is an emergent vascular disease. Currently, its diagnosis depends on clinical and radiological investigations but lacking of serum biomarkers. In this study, we aimed to identify potential serum biomarkers for AAD using label-free proteomics approach. A total of 90 serum samples were collected from three groups: patients with acute aortic dissection (AAD, n = 30), patients with acute myocardial infarction (AMI, n = 30), and healthy controls (n = 30), and the first four samples from each group were selected for label-free proteomics analysis. Using label-free approach, a total of 22 differentially expressed proteins were identified in the serum samples of the AAD group, of which 15 were upregulated and 7 were downregulated as compared to the AMI and healthy control groups. The most prominent increased protein was vinculin, which was selected to validate in total samples. The level of vinculin was significantly elevated in AAD patients (15.8 ng/ml, IQR: 9.3-19.9 ng/ml) than that in AMI patients (8.6 ng/ml, IQR:5.3-11.4 ng/ml) and healthy volunteers (5.3 ng/ml, IQR:2.8-7.6 ng/ml), P < 0.0001. Furthermore, the concentration of vinculin both increased in type A and B dissection. At the early stage of AAD, vinculin maintained a high level to 48 hours compared with that of AMI. Our study demonstrated that vinculin may play a role in the early diagnosis of AAD.


Subject(s)
Aortic Aneurysm/diagnosis , Aortic Dissection/diagnosis , Biomarkers/blood , Myocardial Infarction/diagnosis , Proteome/analysis , Proteomics/methods , Vinculin/blood , Aortic Dissection/blood , Aortic Aneurysm/blood , Case-Control Studies , Diagnosis, Differential , Early Diagnosis , Female , Humans , Male , Middle Aged , Myocardial Infarction/blood
9.
J Thorac Dis ; 12(12): 7117-7126, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33447400

ABSTRACT

BACKGROUND: This study analyzes the outcomes of a one-stage hybrid procedure combining thoracic endovascular aortic repair (TEVAR) with extra-anatomic bypass in patients with distal aortic arch disease. METHODS: This retrospective study collected 103 hybrid procedures combining TEVAR with extra-anatomic bypass (mean age, 62.2±9.3 years; 90 males) performed from January 2009 to January 2019 at Beijing Anzhen Hospital. We analyzed 30-day and mid-term outcomes including survival rate and the incidence of stroke, spinal cord injury (SCI), and endoleak. RESULTS: Five deaths (4.6%) occurred within 30 days, including type I endoleak in Zone 1 (n=1), hemorrhagic shock (n=1), stroke (n=2), and stent migration (n=1). Two patients developed SCI. The median follow-up time was 39.5 (interquartile range, 13.6-69.0) months. In all, 14 late deaths occurred; these were due to stroke (n=2), severe pneumonia (n=1), aortic rupture caused by type I endoleak (n=3), and sudden death (n=8). Six late endoleaks occurred including three type I and one type II in Zone 1 and two type I in Zone 2. In a competing risks analysis, the incidences of reintervention at 7 years, late death, and survival without reintervention were 8%, 22%, and 70%, respectively. In a Cox risk model, stroke (HR, 21.602; 95% CI: 2.798-166.796; P=0.003) was the only risk factor for 30-day mortality. Stroke (HR, 19.484; 95% CI: 5.245-72.380; P<0.001), SCI (HR, 15.548; 95% CI: 2.754-87.786; P=0.002), and endoleak (HR, 4.626; 95% CI: 1.068-20.040; P=0.041) were independent risk factors for long-term mortality. CONCLUSIONS: The one-stage hybrid procedure provides acceptable mid-term results with good mid-term patency of extra-anatomic bypass. Strict selection of patients suitable for hybrid repair can effectively improve the survival rate and reduce the incidence of complications. At the same time, close follow-up patients should receive close long-term follow-up after hybrid procedure.

10.
J Thorac Cardiovasc Surg ; 159(6): 2202-2213.e4, 2020 06.
Article in English | MEDLINE | ID: mdl-31376997

ABSTRACT

OBJECTIVE: Cervical aortic arch (CAA) is rare and difficult to repair. Clinical experience is limited. We report the surgical techniques and midterm outcomes in 35 patients with CAA based on an alternative classification scheme. METHODS: Of 35 patients with CAA, 30 (85.7%) had left-sided aortic arch and 5 had (14.3%) right-sided aortic arch (all 5 had a vascular ring). Mean age was 34.2 ± 13.1 years, 23 were female (65.7%), and 18 were asymptomatic (51.4%). Surgical access and procedure were chosen according to an alternative classification scheme that is based on the presence or absence of vascular ring and relationship of descending aorta to the side of the aortic arch. In the left-sided aortic arch group, aortic arch reconstruction though median sternotomy was performed in 15 patients, and distal arch and descending thoracic aortic replacement via left thoracotomy in 15 patients. In the right-sided aortic arch group, ascending-to-descending aortic bypass was done via median sternotomy in 2 patients and right thoracotomy in 1, and distal arch and descending thoracic aortic replacement via right thoracotomy in 2 patients. RESULTS: Neither death nor spinal cord injury occurred. Left recurrent laryngeal nerve injury, prolonged ventilation, and reexploration for bleeding occurred in 1 each. In 11 patients with coarctation, the upper-lower limb gradient decreased significantly postoperatively (from 34.0 ± 12.7 to 10.2 ± 2.7 mm Hg; P < .01). The diseased aortic segment was excluded in 34 patients, except 1 with residual aneurysm in the proximal descending thoracic aorta. Follow-up was complete in 100% at mean 4.4 ± 2.0 years. No late death, limb ischemia, or stroke occurred. Endovascular repair was performed in 1 patient, and ascending aortic dilation occurred in 1 patient. The residual aorta remained nondilated in 33 patients. Aortic grafts were patent in 100%, with no anastomotic leak or pseudoaneurysm. At 6 years, the incidences of death, aortic events, and event-free survival were 0%, 6.5%, and 93.5%, respectively. CONCLUSIONS: Open repair of CAA can achieve favorable early and midterm outcomes. Surgical accesses and procedures should be chosen based on type of CAA, anatomic variations and associated anomalies. Our alternative categorization scheme of CAA is intuitive and comprehensive, which may facilitate classification and surgical decision making.


Subject(s)
Aorta, Thoracic/surgery , Blood Vessel Prosthesis Implantation , Sternotomy , Thoracotomy , Vascular Ring/surgery , Adolescent , Adult , Aorta, Thoracic/abnormalities , Aorta, Thoracic/diagnostic imaging , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Clinical Decision-Making , Female , Humans , Male , Middle Aged , Patient Selection , Postoperative Complications/therapy , Progression-Free Survival , Retrospective Studies , Risk Factors , Sternotomy/adverse effects , Sternotomy/mortality , Thoracotomy/adverse effects , Thoracotomy/mortality , Time Factors , Vascular Ring/classification , Vascular Ring/diagnostic imaging , Vascular Ring/mortality , Young Adult
11.
World J Clin Cases ; 7(18): 2843-2850, 2019 Sep 26.
Article in English | MEDLINE | ID: mdl-31616701

ABSTRACT

BACKGROUND: Aortic dissection during pregnancy is a rare but life-threatening event for mothers and fetuses. It often occurs in the third trimester of pregnancy and the postpartum period. Most patients have connective tissue diseases such as Marfan syndrome. Thus, the successful repair of a sporadic aortic dissection with maternal and fetal survival in the early second trimester is extremely rare. CASE SUMMARY: A 28-year-old woman without Marfan syndrome presented with chest pain at the 16th gestational week. Aortic computed tomographic angiography confirmed an acute type A aortic dissection (TAAD) with aortic arch and descending aorta involvement. Preoperative fetal ultrasound confirmed that the fetus was stable in the uterus. The patient underwent total arch replacement with a frozen elephant trunk using moderate hypothermic circulatory arrest with the fetus in situ. The patient recovered uneventfully and continued to be pregnant after discharge. At the 38th gestational week, she delivered a healthy female infant by cesarean section. After 2.5 years of follow-up, the patient is uneventful and the child's development is normal. CONCLUSION: A fetus in the second trimester may have a high possibility of survival and healthy growth after aortic arch surgery.

12.
J Thorac Dis ; 10(9): 5376-5383, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30416785

ABSTRACT

BACKGROUND: Several methods of arch vessel reconstruction, such as en bloc (island) and branched graft techniques, have been proposed to treat aortic arch pathologies during total arch replacement (TAR). We seek to review our experience with modified en bloc technique and left subclavian (LSCA)-left carotid artery (LCCA) transposition in TAR and frozen elephant trunk (FET) procedure for chronic type A aortic dissection (CTAAD). METHODS: From September 2010 to September 2016, 35 consecutive patients with CTAAD underwent modified en bloc arch reconstruction with LSCA-LCCA transposition during TAR and FET procedure. Computed tomographic angiography (CTA) was performed during follow-up. RESULTS: In-hospital mortality was 5.7% (2/35). No neurological deficit or spinal cord injury occurred. Re-exploration for bleeding and continuous renal replacement therapy were required in 2 patients each (5.7%). Follow-up was complete in 100% for a mean duration of 4.1±1.8 years (range, 0.5-6.7 years). One patient experienced a transient stroke and thoracoabdominal aortic replacement was performed in 1. There were 2 late non-cardiac deaths. Survival was 87.9% (95% CI, 70.7-95.3%) at 6 years. At 6 years, the incidence was 3% for reoperation, 12% for late death, and 85% of patients were alive without reoperation. The anastomosis between the LSCA and LCCA was patent in 100%. CONCLUSIONS: Acceptable early and mid-term outcomes were achieved for patients with chronic type A dissection using en bloc technique with LSCA-LCCA transposition during TAR and FET procedure. This technique may be an alternative approach to chronic type A dissection in selected patients.

13.
Bioorg Med Chem Lett ; 22(21): 6591-5, 2012 Nov 01.
Article in English | MEDLINE | ID: mdl-23010272

ABSTRACT

On the purpose of searching for the structure-activity relationship (SAR) and obtaining novel anti-platelet drugs, 41 4-methoxybenzene-1,3-isophthalamides have been described the synthesis process and in vitro activities on anti-platelet aggregation. The target compounds have been classified into four series: series 1 (ortho-substituted phenyl: 1a-1j), series 2 (meta-substituted phenyl: 2a-2k), series 3 (para-substituted phenyl: 3a-3l) and series 4 (aromatic of no substituted group and aromatic heterocyclic substituted groups: 4a-4h). The chemical structures of the target compounds were confirmed by MS, IR, (1)H NMR, and their in vitro activities on anti-platelet aggregation were tested and assessed by using Born test. The result showed that thirteen compounds 1c, 1d, 1i, 1j, 2g, 3a, 3c, 3d, 3f, 3h, 3l, 4b and 4c have superior anti-platelet aggregation activities than the reference drug Picotamide.


Subject(s)
Blood Platelets/drug effects , Drug Design , Phthalimides/chemical synthesis , Phthalimides/pharmacology , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Delivery Systems , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Phthalic Acids/chemistry , Phthalic Acids/pharmacology , Phthalimides/chemistry , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/chemistry , Rats
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