scholarly journals Genesis of epicardial adipocytes and its association with progenitor markers, muscarinic receptor type 3 and b-blockers intake in patients with cardiovascular disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
X Fu ◽  
C Almenglo ◽  
M Couselo-Seijas ◽  
A L Fernandez ◽  
J M Martinez-Cereijo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Muscarinic Receptor ◽  
Heart Surgery ◽  
Ex Vivo ◽  
Subcutaneous Fat ◽  
Open Heart Surgery ◽  
Receptor Type ◽  
Epicardial Fat ◽  
Eat Cells ◽  
Β Blockers

Abstract Introduction Epicardial fat thickness or volume was found to be associated with cardiovascular disease (CVD). Our aim was to study the epicardial adipocyte-progenitors' markers and its association with cholinergic or adrenergic activity in patients with cardiovascular disease. Materials and methods We have included epicardial adipose tissue (EAT) biopsies from 29 patients underwent open-heart surgery. From 10 patients (69±5 years old, 31±8 kg/ m2, 40% CAD, 40% HF, 60% AF, 0% T2DM) stromal cells from epicardial and subcutaneous fat were isolated after collagenase activity and cultured for 14 days and then submitted to adipogenesis for next 14 days. Samples from 19 patients (60±9 years old, 29±4 kg/m2, 42% CAD, 37% HF, 32% AF, 32% T2DM, 53% β-blockers) were used for “ex vivo assays”. Explants were split into equal pieces (100 mg), treated with or without acetylcholine (ACh) for 30 min. Afterwards RNA was isolated and cDNA was amplified by real time PCR. We selected adipocytes progenitors (CD36, PREF1, COL1A1), adipocytes markers (ADIPO, FABP4), muscarinic (muscarinic receptor type 2 (CHRM2) and 3 (CHRM2)) and β-adrenergic receptors (ABRD1, ABRD2 and ABRD3). Gene expression was represented regarding ACTB as 2HK/GEN. Results The stromal vascular cells (SVC) from subcutaneous fat (SAT) had higher expression levels of CD36, PREF1 and COL1A1 than SVC from epicardial fat (EAT). It explains the higher adipocytes markers after adipogenesis induction in SAT than EAT cells. However, an upregulation of fibroblasts markers was detected on EAT. The levels of CD36 and PREF1 in SVC were associated with higher adipogenesis. Although CHRM2 was higher in EAT than SAT SVC, the adipogenesis induction upregulated only CHRM3 (1.48±0.065 vs 1.42±0.036 a.u.) in EAT cells. Thus, this receptor was associated with adipocytes markers in epicardial fat (r=0.777 for CD36 and r=0.746 for FABP4) and incremented in epicardial fat biopsies from patients who were taken β-blockers (1.61±0.011 n=10 vs 1.54±0.097 a.u. n=9; p=0.05) and modulated by ACh treatment (p=0.05). Conclusions Our results showed that CD36 and PREF1 in epicardial SVC are adipocytes progenitors. The higher presence of adipocytes markers is associated with higher levels of muscarinic receptor (CHRM3), which are upregulated in epicardial fat from patients who were taken β-blockers and modulated by cholinergic activity. Because a metabolic and lipolytic dysfunction was associated with CHRM3, the sympathetic modulation might play a role in the epicardial adipocytes genesis. Further studies are needed to understand if this mechanism might improve or not future cardiovascular events. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ISCIII (PFIS2020)

Monitoring of r-Hirudin Anticoagulation during Cardiopulmonary Bypass – Assessment of the Whole Blood Ecarin Clotting Time

1997 ◽  
Vol 77 (05) ◽  
pp. 0920-0925 ◽  
Author(s):  
Bernd Pötzsch ◽  
Katharina Madlener ◽  
Christoph Seelig ◽  
Christian F Riess ◽  
Andreas Greinacher ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Whole Blood ◽  
Heart Surgery ◽  
Ex Vivo ◽  
Open Heart Surgery ◽  
Clotting Time ◽  
Blood Samples ◽  
Alternative Approach ◽  
Ecarin Clotting Time

SummaryThe use of recombinant ® hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor Ila assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin- spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 µg/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin- spiked blood samples obtained from 50 healthy blood donors. CV- values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 µg/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.

Techniques in Cardiac Care: Lasers, Stents, and Atherectomy Devices

1990 ◽  
Vol 1 (1) ◽  
pp. 87-109 ◽  
Author(s):  
Marsha Halfman-Franey ◽  
Cathy Coburn
Keyword(s):  
Cardiovascular Disease ◽  
Heart Surgery ◽  
New Technologies ◽  
Open Heart Surgery ◽  
Cardiac Care ◽  
Open Heart ◽  
Endovascular Stents ◽  
Care Nurse ◽  
Critical Care Nurse ◽  
Optimal Patient Care

Various new technologies are currently being investigated to treat cardiovascular disease less invasively than with conventional open heart surgery. Although lasers have been used in other health disciplines, their use in the cardiovascular field is relatively new. Even newer is the use of atherectomy devices and endovascular stents. It is important for the critical care nurse to be knowledgeable concerning these techniques in order to provide optimal patient care.

Abstract 3648: Clinical Cardiovascular Disease in Women is Associated With Increased Epicardial, but Not Subcutaneous Fat Thickness

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Noriko Oyama ◽  
Philimon Gona ◽  
Michael L Chuang ◽  
Rahul R Jhaveri ◽  
Carol J Salton ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Menopausal Status ◽  
Subcutaneous Fat ◽  
Epicardial Fat ◽  
Adult Women ◽  
Increased Risk ◽  
Subcutaneous Fat Thickness ◽  
Fat Thickness ◽  
The Relationship

INTRODUCTION: Visceral adipose tissue, such as epicardial fat, is metabolically active, and may portend increased risk for cardiovascular disease (CVD) compared to subcutaneous fat. Cardiovascular magnetic resonance (CMR) can accurately delineate fat, but data are sparse regarding the relationship of epicardial and subcutaneous fat burden to CVD in community-living adult women. METHODS: 957 women (aged 64± 8 years) in the Framingham Heart Study Offspring cohort, followed by serial examinations since 1974, underwent CMR on a 1.5-T Philips system using an ECG-gated cine SSFP sequence. Epicardial fat thickness (EFT) over the midlevel right ventricle was measured from a 4-chamber view. Suprasternal subcutaneous fat thickness (SFT) was measured at the main pulmonary artery level. We compared EFT and SFT between women with clinical CVD, documented by a physician endpoint committee (+CVD), vs. those without (noCVD) based on Cycle 7 (1998 –2002) clinical data. Differences were assessed by two-sample T-test; ANOVA was used to adjust for age, diabetes, hypertension and menopausal status. RESULTS: The +CVD group comprised 74 (8%) women who were older and more likely to be postmenopausal, diabetic and hypertensive than noCVD women (Table ). EFT was greater in +CVD (10.5 ± 5.1mm) vs. noCVD (8.6 ± 5.2mm) groups, p<0.003. This difference remained significant after adjusting for age, diabetes, hypertension and menopausal status (Table ). No difference in SFT or body mass index was observed between groups (p=NS). CONCLUSIONS: Women with history of clinical CVD have greater EFT than women without CVD, and this difference persists after adjustment for common cardiovascular risk factors. However, subcutaneous fat, as assessed by chest wall adiposity, did not differ between groups. EFT may be a useful marker for cardiovascular risk, and prospective investigation of the relationship between EFT and future risk for CVD is warranted.

The New Era of Cardiac Surgery Hybrid Therapy for Cardiovascular Disease

2010 ◽  
Vol 5 (6) ◽  
pp. 388-393 ◽  
Author(s):  
Natalia V. Solenkova ◽  
Ramanan Umakanthan ◽  
Marzia Leacche ◽  
David X. Zhao ◽  
John G. Byrne
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Coronary Artery Bypass Grafting ◽  
Coronary Artery Bypass ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Open Heart Surgery ◽  
Bypass Grafting ◽  
Hybrid Strategy ◽  
Artery Bypass Grafting

Surgical therapy for cardiovascular disease carries excellent long-term outcomes but it is relatively invasive. With the development of new devices and techniques, modern cardiovascular surgery is trending toward less invasive approaches, especially for patients at high risk for traditional open heart surgery. A hybrid strategy combines traditional surgical treatments performed in the operating room with treatments traditionally available only in the catheterization laboratory with the goal of offering patients the best available therapy for any set of cardiovascular diseases. Examples of hybrid procedures include hybrid coronary artery bypass grafting, hybrid valve surgery and percutaneous coronary intervention, hybrid endocardial and epicardial atrial fibrillation procedures, and hybrid coronary artery bypass grafting/carotid artery stenting. This multi-disciplinary approach requires strong collaboration between cardiac surgeons, vascular surgeons, and interventional cardiologists to obtain optimal patient outcomes.

Effect of INS50589, a Reversible ADP-Receptor Antagonist, on Platelet Function and Blood Loss in a Canine Model of Cardiopulmonary Bypass.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2172-2172
Author(s):  
Arthur P. Bode ◽  
Christopher S. Crean ◽  
You-Su Sun ◽  
Wiley Nifong ◽  
Jose L. Boyer ◽  
...  
Keyword(s):  
Treatment Group ◽  
Blood Loss ◽  
Receptor Antagonist ◽  
Platelet Function ◽  
Whole Blood ◽  
Heart Surgery ◽  
Ex Vivo ◽  
Open Heart Surgery ◽  
Canine Model ◽  
Open Heart

Abstract Open-heart surgery performed with cardiopulmonary extracorporeal bypass (CPB) of anticoagulated blood often is complicated by excessive postoperative hemorrhage due to an acquired platelet function defect and thrombocytopenia inherent to the procedure. One strategy for reducing excessive blood loss is to protect the platelets pharmacologically from activation and damage during the surgical procedure and the CPB, but most inhibitors of platelet activation used in this way would exacerbate bleeding because of the duration of their effect. INS50589 is a competitive and selective P2Y12 receptor antagonist in development by Inspire Pharmaceuticals Inc. Previous studies in normal dogs indicate that 20μM ADP induced ex vivo whole blood platelet aggregation is completely inhibited by the administration of INS50589 and that the effect is quickly reversed upon discontinuation of the administration. This drug is now being tested for efficacy and safety in a canine model of CPB established at East Carolina University. Subjects in the range of 20–30 kg are prepared by sternotomy for extracorporeal recirculation of blood after systemic heparinization. CPB occurs for ninety minutes, followed by weaning from the pump and maintenance for a four hour postoperative period. INS50589 was administered by continuous infusion at a rate of 17 mg/kg/min at initiation of sternotomy and throughout CPB until weaned. Special testing in all subjects includes ex vivo whole blood aggregometry with two doses of ADP, thromboelastography with the TEG® ADP Mapping kit, bleeding times using a 23 gauge puncture of the exposed jugular vein, and measurements of blood loss from the surgical fields. In the placebo treated group, there was a significant loss of platelet response to ADP during CPB that remained in the post-op period at approx 50% of initial values; in contrast, the drug-treated subjects show post-op recovery of ADP response to within 90% of initial values (p<0.01). The vessel bleeding time (VBT) within both groups was greatly prolonged during CPB. Preliminary analysis suggests that in the post-operative period the VBT returned to baseline values after the infusion was discontinued; however, the return was faster in the INS50589-treated animals when compared with the placebo group. The volume of post-operative blood loss was variable but appears to be less in the drug-treatment group versus placebo controls. When adjusted on the basis of red cell mass in the shed blood per body weight the difference was significant (4.78±1.99e10 vs. 10.1±2.91e10 red blood cells/kg), p <0.05. Other preliminary findings in the treatment group included a lesser CPB-related decrease in platelet count, a higher average hematocrit, higher post-op fibrinogen concentration, and a more stable post-op course. These preliminary findings suggest that INS50589 should be effective in protecting platelet function and reducing blood loss in human patients undergoing open-heart surgery.

Small extracellular vesicles from epicardial fat of patients with atrial fibrillation induce inflammation, fibrosis and re-entrant arrhythmias

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
O Shaihov-Teper ◽  
E Ram ◽  
R Brzezinski ◽  
D Volvovitch ◽  
E Zuroff ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Extracellular Vesicles ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Induced Pluripotent Stem Cell ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Size Exclusion ◽  
Epicardial Fat ◽  
Atrial Remodeling

Abstract Background and aim Epicardial fat (eFat) has been linked to atrial remodeling and fibrillation (AF). Small extracellular vesicles (sEVs) are heterogeneous membrane vesicles released by all cell types. They can both protect and damage tissues by the delivery of multiple different messengers. Surprisingly, the role of sEVs in the pathogenesis of AF has not been studied. Thus, we aimed to determine whether sEVs derived from eFat play a role in the pathogenesis of AF. Methods and results We collected eFat specimens from patients with and without chronic or paroxysmal AF undergoing open-heart surgery. Isolated eFat specimens were cut into small pieces and incubated as organ cultures. We isolated sEVs from the medium of the explant by differential ultra-centrifugation, high-density gradient or size exclusion chromatography (SEC), and characterized vesicle size distribution, morphology, specific markers, histology and molecular cargo. Immunostaining for macrophage accumulation, fibrosis and apoptosis confirmed the pro-inflammatory and pro-fibrotic properties of eFat sEVs from patients with AF (Fig. 1). eFat sEVs labeled with PKH26 were massively up taken by endothelial cells (Fig. 2). Real-time PCR showed an increased level of oxidative stress genes in endothelial cells. eFat sEVs from patients with AF caused more fibrosis after injection into rat hearts than those without AF. (Fig. 3). Finally, while eFat sEVs from patients with and without AF induced shorter action potential duration, only eFat sEVs from patients with AF induced sustained re-entry (rotor) in human induced pluripotent stem cell (iPS)-derived cardiomyocytes (Fig. 4) Conclusion We show, for the first time, that sEVs from eFat of patients with AF demonstrate unique pro-inflammatory, pro-fibrotic and pro-arrhythmic properties. Our findings suggest that eFat sEVs can induce cellular, molecular and electrophysiological remodeling that can subsequently lead to the development of AF. Funding Acknowledgement Type of funding source: None

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