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1.
Open Forum Infect Dis ; 11(5): ofae225, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38751899

RESUMEN

Background: This study aimed to characterize the demographics, microbiology, management and treatment outcomes of mediastinitis according to the origin of the infection. Methods: This retrospective observational study enrolled patients who had mediastinitis diagnosed according to the criteria defined by the Centers for Disease Control and Prevention and were treated in Strasbourg University Hospital, France, between 1 January 2010 and 31 December 2020. Results: We investigated 151 cases, including 63 cases of poststernotomy mediastinitis (PSM), 60 cases of mediastinitis due to esophageal perforation (MEP) and 17 cases of descending necrotizing mediastinitis (DNM). The mean patient age (standard deviation) was 63 (14.5) years, and 109 of 151 patients were male. Microbiological documentation varied according to the origin of the infection. When documented, PSM cases were mostly monomicrobial (36 of 53 cases [67.9%]) and involved staphylococci (36 of 53 [67.9%]), whereas MEP and DNM cases were mostly plurimicrobial (38 of 48 [79.2%] and 8 of 12 [66.7%], respectively) and involved digestive or oral flora microorganisms, respectively. The median duration of anti-infective treatment was 41 days (interquartile range, 21-56 days), and 122 of 151 patients (80.8%) benefited from early surgical management. The overall 1-year survival rate was estimated to be 64.8% (95% confidence interval, 56.6%-74.3%), but varied from 80.1% for DNM to 61.5% for MEP. Conclusions: Mediastinitis represents a rare yet deadly infection. The present cohort study exhibited the different patterns observed according to the origin of the infection. Greater insight and knowledge on these differences may help guide the management of these complex infections, especially with respect to empirical anti-infective treatments.

2.
Eur J Cardiothorac Surg ; 65(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38466938

RESUMEN

OBJECTIVES: The aim of this study was to assess the safety of early chest tube removal (CTR) protocol on the 1st postoperative day (POD1) of our Enhanced Recovery After Surgery (ERAS) programme by comparing the risk of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality. METHODS: All consecutive patients undergoing elective coronary revascularization and/or valve surgery between 2015 and 2021 were assessed in terms of their perioperative management pathways: conventional standard of care (control group) versus standardized systematic perioperative ERAS programme including an early CTR on POD1 (ERAS group). A propensity score matching was applied. The primary end-point was a composite of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality. RESULTS: A total of 3153 patients were included. Propensity score analysis resulted in 2 groups well-matched pairs of 1026 patients. CTR on POD1 was significantly increased from 29.5% in the control group to 70.3% in the ERAS group (P < 0.001). The incidence of the primary end-point was 6.4% in the control group and 6.9% in the ERAS group (P = 0.658). Patients in the ERAS group, as compared with control group, had significant lower incidence of bronchopneumonia (9.0% vs 13.5%; P = 0.001) and higher incidence of mechanical ventilation ≤6 h (84.6% vs 65.2%; P < 0.001), length of intensive care unit ≤1 day (61.2% vs 50.8%; P < 0.001) and hospital ≤6 days (67.3% vs.43.2%; P < 0.001). CONCLUSIONS: CTR on POD1 protocol can be safely incorporated into a standardized systematic ERAS programme, enabling early mobilization, and contributing to the improvement of postoperative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: Ethics committee of the French Society of Thoracic and Cardio-Vascular Surgery (CERC-SFCTCV-2022-09-13_23140).


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Derrame Pericárdico , Neumotórax , Humanos , Tubos Torácicos , Resultado del Tratamiento , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control
3.
Artículo en Inglés | MEDLINE | ID: mdl-37611846

RESUMEN

OBJECTIVE: To evaluate the effect of a perioperative systematic standardized enhanced recovery after surgery (ERAS) program for patients undergoing isolated elective coronary artery bypass grafting (CABG) in terms of mortality, hospital morbidities, and length of stay. METHODS: From January 2015 to September 2020, 1101 patients underwent isolated elective CABG. Our standardized systematic ERAS program was implemented in November 2018. Propensity score matching resulted in well-matched pairs of 362 patients receiving standard perioperative care (control group) and 362 patients on the ERAS program (ERAS group). There were no significant intergroup differences in preoperative and operative data except for the normothermia rate, which was significantly greater in the ERAS group (P < .001). The primary outcome was 3-year mortality. The secondary outcomes were hospital morbidities and length of stay. RESULTS: In-hospital and 3-year mortality did not differ between the 2 groups. The ERAS program was associated with a significant relative risk decrease in mechanical ventilation duration (-53.1%, P = .003), length of intensive care unit stay (-28.0%, P = .015), length of hospital stay (-10.5%, P = .046), bronchopneumonia (-51.5%, P < .001), acute respiratory distress syndrome (-50.8%, P = .050), postoperative delirium (-65.4%, P = .011), moderate-to-severe acute kidney injury (-72.0%, P = .009), 24-hour chest tube output (-26.4%, P < .001), and overall red blood cell transfusion rate (-32.4%, P = .005) compared with the control group. CONCLUSIONS: A systematic standardized ERAS program for low-risk patients undergoing isolated elective CABG was associated with a significant improvement in postoperative outcomes, reduction in red blood cell transfusion, shorter lengths of intensive care unit and hospital stays, and comparable long-term mortality.

4.
Eur J Cardiothorac Surg ; 63(5)2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37014362

RESUMEN

OBJECTIVES: Evidence regarding the benefits of an enhanced recovery after cardiac surgery (ERACS) programme is lacking. The aim of this study was to analyse the impact of a systematic standardized ERACS programme for patients undergoing isolated elective surgical aortic valve replacement (SAVR) for aortic stenosis in terms of hospital mortality and morbidity, patient blood management and length of stay. METHODS: Patients undergoing isolated elective SAVR for aortic stenosis between 2015 and 2020 were identified from our database (n = 941). The standardized systematic ERACS programme was implemented in November 2018. Propensity score matching indicated that 259 patients would receive standard perioperative care (control group) and 259 patients would receive the ERACS programme (ERACS group). The primary outcome was hospital mortality. The secondary outcomes were hospital morbidity, patient blood management and length of stay. RESULTS: Both groups had similar hospital mortality rates (0.4%). The ERACS group had a significantly lower troponin I peak level (P < 0.001), a larger proportion of improved perioperative left ventricular ejection fractions (P = 0.001), a lower incidence of bronchopneumonia (P = 0.030), a larger proportion of patients with mechanical ventilation <6 h (P < 0.001), a lower incidence of delirium (P = 0.028) and less acute renal failure (P = 0.013). The ERACS group had a significantly lower rate of red blood cell transfusions (P = 0.002). The intensive care unit stay was significantly shorter in the ERACS group than in the control group (P = 0.039). CONCLUSIONS: The standardized systematic ERACS programme significantly improved postoperative outcomes and should become the reference for the perioperative care pathway for patients undergoing SAVR.


Asunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Válvula Aórtica/cirugía , Factores de Riesgo , Resultado del Tratamiento , Estenosis de la Válvula Aórtica/cirugía
5.
J Clin Med ; 11(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36498821

RESUMEN

INTRODUCTION: The mitochondrial function of circulating peripheral blood mononuclear cells (PBMCs) is an interesting new approach to cardiac diseases. Thus, PBMC's mitochondrial respiration decreases in relation to heart failure severity. However, no data are available on heart-transplanted patients (Htx). POPULATION AND METHODS: We determined PBMCs mitochondrial respiration by high-resolution respirometry (Oroboros Instruments) and superoxide anion production using electron paramagnetic resonance (Bruker-Biospin) in 20 healthy subjects and 20 matched Htx and investigated clinical, biological, echocardiographic, coronarography and biopsy characteristics. RESULTS: PBMCs mitochondrial respiratory chain complex II respiration was decreased in Htx (4.69 ± 0.84 vs. 7.69 ± 1.00 pmol/s/million cell in controls and Htx patients, respectively; p = 0.007) and complex IV respiration was increased (24.58 ± 2.57 vs. 15.68 ± 1.67 pmol/s/million cell; p = 0.0035). Superoxide anion production was also increased in Htx (1.47 ± 0.10 vs. 1.15 ± 0.10 µmol/min; p = 0.041). The leucocyte-to-lymphocyte ratio was increased in Htx, whom complex II correlated with leucocyte number (r = 0.51, p = 0.02) and with the left ventricular posterior wall peak early diastolic myocardial velocity (r = -0.62, p = 0.005). Complex IV was increased in the two patients with acute rejection and correlated negatively with Htx's isovolumetric relation time (r = -0.45, p = 0.045). DISCUSSION: Although presenting with normal systolic function, Htx demonstrated abnormal PBMC's mitochondrial respiration. Unlike immunosuppressive therapies, subclinical diastolic dysfunction might be involved in these changes. Additionally, lymphopenia might reduce complex II, and acute rejection enhances complex IV respirations. CONCLUSION: PBMC's mitochondrial respiration appears modified in Htx, potentially linked to cellular shift, mild diastolic dysfunction and/or acute rejection.

6.
Ann Thorac Surg ; 114(5): e371-e373, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35077671

RESUMEN

Direct intracardiac extension of abdominal malignant diseases represents a rare but challenging situation. Removal of the intracardiac extension requires cardiopulmonary bypass with systemic anticoagulation, which could potentially increase the risk of bleeding if it is associated with liver resection. This report describes a 2-stage surgical approach for malignant disease with intracardiac extension in a high-risk patient. Atrial thrombectomy was performed first, followed by right portal vein embolization. Four months after the cardiac surgical procedure, the patient underwent right hepatectomy extended to segment 1, the right adrenal gland, and the retrohepatic inferior vena cava under venovenous bypass. The advantages and drawbacks of this approach are discussed.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Neoplasias Hepáticas , Humanos , Carcinoma Corticosuprarrenal/cirugía , Carcinoma Corticosuprarrenal/complicaciones , Carcinoma Corticosuprarrenal/patología , Hepatectomía/métodos , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Atrios Cardíacos/cirugía , Atrios Cardíacos/patología , Neoplasias de la Corteza Suprarrenal/cirugía , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/patología , Anticoagulantes , Neoplasias Hepáticas/patología
7.
J Thorac Dis ; 12(5): 2654-2662, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32642173

RESUMEN

BACKGROUND: Left ventricular assist device (LVAD)-associated infections are major complications that can lead to critical outcomes. The aims of this study were to assess the incidence of and to determine the risk factors for LVAD-associated infections. METHODS: We included all consecutive patients undergoing LVAD implantation between January 1, 2010, and January 1, 2019, in a single institution. Infection-related data were retrospectively collected by review of patient's medical files. LVAD-associated infections were classified into three categories: percutaneous driveline infections, pocket infections and pump and/or cannula infections. RESULTS: We enrolled 72 patients. Twenty-one (29.2%) patients presented a total of 32 LVAD-associated infections. Eight (38.1%) patients had more than one infection. Five (62.5%) pocket infections and one (50.0%) pump and/or cannula infection were preceded by a driveline infection. The median delay between the operation and LVAD-associated infection was 6.5 (1.4-12.4) months. The probability of having a LVAD-associated infection at one year after receiving an implant was 26.6% (95% CI: 17.5-40.5%). Percutaneous driveline infections represented 68.7% of all LVAD-associated infections. Staphylococcus aureus and coagulase-negative staphylococci were the predominant bacteria in LVAD-associated infections (53.1% and 15.6%, respectively). Hospital length of stay (sdHR =1.22 per 10 days; P=0.001) and postoperative hemodialysis (sdHR =0.17; P=0.004) were statistically associated with infection. Colonization with multidrug-resistant bacteria was more frequent in patients with LVAD-associated infections than in others patients (42.9% vs. 15.7%; P=0.013). CONCLUSIONS: LVAD-associated infections remain an important complication and are mostly represented by percutaneous driveline infections. Gram-positive cocci are the main pathogens isolated in microbiological samples. Patients with LVAD-associated infections are more frequently colonized with multidrug-resistant bacteria.

8.
J Thorac Dis ; 12(4): 1496-1506, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32395287

RESUMEN

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with significant mortality and morbidity. The objective of this study was to determine pre- and postoperative risk factors associated with the occurrence of RVF after LVAD implantation. METHODS: This retrospective study included 68 patients who received LVADs between 2010 and 2018 either for bridge to transplant (40 patients, 58.8%) or bridge to destination therapy (28 patients, 41.2%). RVF after LVAD implantation was defined according to the INTERMACS classification. The primary endpoint was the occurrence of RVF. The secondary endpoints were hospital mortality and morbidity and long-term survival. RESULTS: The majority of patients (61.8%) had an INTERMACS profile 1 (36.8%) or 2 (25.0%). The LVAD was implanted either by sternotomy (37 patients, 54.4%) or thoracotomy (31 patients, 45.6%). RVF after LVAD implantation was observed in 32 patients (47.1%). In univariate analysis, an elevated serum glutamic oxaloacetic transaminase (SGOT) (P=0.028) and a high preoperative vasoactive inotropic score (VIS) (P=0.028) were significantly associated with an increased risk of RVF, whereas the implantation of LVAD through a thoracotomy approach was associated with a significant reduction in this risk (P=0.006). The multivariate analysis demonstrated that only the thoracotomy approach was significantly associated with decreased risk of RVF (odds ratio =0.33, 95% confidence interval: 0.17-0.96; P=0.042). Hospital mortality was 53.1% and 5.6% in the RVF and control groups, respectively (P<0.0001). The incidence of stroke and postoperative acute renal failure were significantly increased in the RVF group compared with the control group. The survival after LVAD implantation was 33.5%±9.0% and 85.4%±6.0% at 1 year in the RVF and control groups, respectively (P<0.0001). CONCLUSIONS: LVAD implantation by thoracotomy significantly reduced the risk of postoperative RVF. This surgical approach should, therefore, be favored.

10.
Infection ; 48(1): 91-97, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31520396

RESUMEN

BACKGROUND: Streptococci involved in infective endocarditis (IE) primarily comprise alpha- or non-hemolytic streptococci (ANHS). Moreover, beta-hemolytic streptococci (BHS) can be involved, and guidelines recommend the addition of gentamicin for the first 2 weeks of treatment and the consideration of early surgery in such cases. This study compared the morbidity and mortality associated with IE depending on the microorganisms involved (BHS, ANHS, staphylococci, and enterococci). METHODS: We conducted a retrospective observational study between 2012 and 2017 in a single hospital in France. The endpoints were overall in-hospital mortality, 1-year mortality and the occurrence of complications. RESULTS: We analyzed 316 episodes of definite IE including 150 (38%), 96 (25%), 46 (12%), and 24 cases (6%) of staphylococcal, ANHS, enterococcal, and BHS IE, respectively. In-hospital mortality was significantly higher in the staphylococcal (n = 40; 26.7%) and BHS groups (n = 6; 25.0%) than in the ANHS (n = 9; 9.4%) and enterococcal groups (n = 5; 10.9%) (all p < 0.01). The rates of septic shock and cerebral emboli were also higher in the BHS group than in the ANHS group [n = 7 (29.2%) vs. n = 3 (3.1%), p < 0.001; n = 7 (29.2%) vs. n = 12 (12.5%); p = 0.05, respectively]. CONCLUSION: This study confirmed that BHS IE has a more severe prognosis than ANHS IE. The virulence of BHS may be similar to that of staphylococci, justifying increased monitoring of these patients and more 'aggressive' treatments such as early surgery.


Asunto(s)
Endocarditis Bacteriana/epidemiología , Infecciones Estreptocócicas/epidemiología , Streptococcus/fisiología , Streptococcus/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/mortalidad , Enterococcus/fisiología , Femenino , Francia/epidemiología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Estudios Retrospectivos , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus/fisiología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/mortalidad , Virulencia , Adulto Joven
11.
J Clin Med ; 9(1)2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31878008

RESUMEN

BACKGROUND: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear. AIMS: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR). METHODS: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis. RESULTS: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, p = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, p = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, p = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, p = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. Conclusions: The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.

12.
Open Forum Infect Dis ; 6(9): ofz308, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31660397

RESUMEN

BACKGROUND: Infective endocarditis (IE) remains a severe disease with a high mortality rate. Therefore, guidelines encourage the setup of a multidisciplinary group in reference centers. The present study evaluated the impact of this "Endocarditis Team" (ET). METHODS: We conducted a monocentric observational study at Strasbourg University Hospital, Strasbourg, France, between 2012 and 2017. The primary end point was in-hospital mortality. Secondary end points were 6-month and 1-year mortality, surgery rate, time to surgical procedure, duration of effective antibiotic therapy, length of in-hospital stay, and sequelae. We also assessed predictors of in-hospital mortality. RESULTS: We analyzed 391 episodes of IE. In the post-ET period, there was a nonsignificant decrease in in-hospital mortality (20.3% vs 14.7%, respectively; P = .27) and sequelae, along with a significant reduction in time to surgery (16.4 vs 10.3 days, respectively; P = .049), duration of antibiotic therapy (55.2 vs 47.2 days, respectively; P < .001), and length of in-hospital stay (40.6 vs 31.9 days, respectively; P < .01). In a multivariate analysis, the post-ET period was positively associated with survival (odds ratio, 0.45; 95% confidence interval, 0.20-0.96; P = .048). CONCLUSIONS: This multidisciplinary approach exerted a positive impact on the management of IE and should be considered in all hospitals managing IE.

13.
Eur J Clin Microbiol Infect Dis ; 38(9): 1753-1763, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31187307

RESUMEN

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).


Asunto(s)
Endocarditis/epidemiología , Infecciones Relacionadas con Prótesis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/microbiología , Bacterias/aislamiento & purificación , Endocarditis/microbiología , Endocarditis/mortalidad , Endocarditis Bacteriana , Femenino , Mortalidad Hospitalaria , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Válvula Mitral/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Estafilocócicas , Estreptococos Viridans , Adulto Joven
14.
Eur J Pharmacol ; 853: 41-48, 2019 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-30878386

RESUMEN

At arterial sites of endothelial denudation and dysfunction, activated platelets contribute to vascular injury through the release of potent contracting factors such as serotonin (5-HT). This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs), known to protect the vascular system, are able to prevent platelets-induced contractile responses in isolated arteries and, if so, to investigate the underlying mechanism and the importance of the omega-3 PUFAs formulation. Porcine coronary arteries (PCA), human internal mammary arteries (IMA) and washed human platelets were prepared and vascular reactivity was studied in organ chambers. In PCA rings, aggregating platelets caused concentration-dependent contractions that were significantly inhibited by the 5-HT2A receptor antagonist ketanserin, and by EPA:DHA 6:1 but not EPA:DHA 1:1 at 0.4% v/v. EPA:DHA 6:1 also prevented the 5-HT-induced contractions but affected only slightly those to the thromboxane A2 analogue U46619. The inhibitory effect of EPA:DHA 6:1 on platelets-induced contractions was not observed in rings without endothelium, and prevented by an eNOS inhibitor but not by inhibitors of endothelium-dependent hyperpolarization. In IMA rings, EPA:DHA 6:1 but not EPA:DHA 1:1 at 0.4% v/v significantly prevented the 5-HT-induced contraction, and induced greater endothelium-dependent relaxations than bradykinin and acetylcholine sensitive to an eNOS inhibitor. EPA:DHA 6:1 strongly inhibits platelets- and 5-HT-induced contractions in PCA rings and those to 5-HT in IMA rings most likely through an increased endothelial formation of NO. These findings suggest that the omega-3 PUFAs EPA:DHA 6:1 formulation may be of interest to prevent platelets-induced vascular injury at arterial sites of endothelial dysfunction.


Asunto(s)
Plaquetas/fisiología , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Arterias Mamarias/efectos de los fármacos , Óxido Nítrico/biosíntesis , Serotonina/metabolismo , Vasoconstricción/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Animales , Ácidos Docosahexaenoicos/química , Composición de Medicamentos , Ácido Eicosapentaenoico/química , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Humanos , Masculino , Arterias Mamarias/fisiología , Persona de Mediana Edad , Porcinos
15.
Pharmacol Res ; 140: 33-42, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30208338

RESUMEN

Heart valve disease (HVD) is a complex entity made by different pathological processes that ultimately lead to the abnormal structure and disorganization of extracellular matrix proteins resulting to dysfunction of the leaflets. At its final evolutionary step, treatments are limited to the percutaneous or surgical valve replacement, whatever the original cause of the degeneration. Understanding early molecular mechanisms that regulate valve interstitial cells remodeling and disease progression is challenging and could pave the way for future drugs aiming to prevent and/or reverse the process. Some valve degenerative processes such as the carcinoid heart disease, drug-induced valvulopathy and degenerative mitral valve disease in small-breed dogs are clearly linked to serotonin. The carcinoid heart is typically characterized by a right-sided valve dysfunction, observed in patients with carcinoid tumors developed from serotonin-producing gut enterochromaffin cells. Fenfluramine or ergot derivatives were linked to mitral and aortic valve dysfunction and share in common the pharmacological property of being 5-HT2B receptor agonists. Finally, some small-breed dogs, such as the Cavalier King Charles Spaniel are highly prone to degenerative mitral valve disease with a prevalence of 40% at 4 years-old, 70% at 7 years-old and 100% in 10-year-old animals. This degeneration has been linked to high serum serotonin, 5-HT2B receptor overexpression and SERT downregulation. Through the comprehension of serotonergic mechanisms involved into these specific situations, new therapeutic approaches could be extended to HVD in general. More recently, a serotonin dependent/ receptor independent mechanism has been suggested in congenital mitral valve prolapse through the filamin-A serotonylation. This review summarizes clinical and molecular mechanisms linking the serotonergic system and heart valve disease, opening the way for future pharmacological research in the field.


Asunto(s)
Enfermedades de las Válvulas Cardíacas/fisiopatología , Válvulas Cardíacas/fisiología , Serotonina/fisiología , Animales , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Humanos
16.
Ann Thorac Surg ; 105(1): 329, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29233334
17.
Ann Thorac Surg ; 104(4): 1433-1434, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28935310
18.
Br J Pharmacol ; 174(22): 4123-4139, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28806488

RESUMEN

BACKGROUND AND PURPOSE: Valvular heart disease (VHD) is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the 5-HT system is associated with VHD. Here, we investigated the contribution of 5-HT receptors in a model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens, dexfenfluramine and benfluorex. EXPERIMENTAL APPROACH: Nordexfenfluramine was infused chronically (28 days) in mice ((WT and transgenic Htr2B -/- , Htr2A -/- , and Htr2B/2A -/- ) to induce mitral valve lesions. Bone marrow transplantation was also carried out. Haemodynamics were measured with echocardiography; tissues and cells were analysed by histology, immunocytochemistry, flow cytometry and RT -qPCR. Samples of human prolapsed mitral valves were also analysed. KEY RESULTS: Chronic treatment of mice with nordexfenfluramine activated 5-HT2B receptors and increased valve thickness and cell density in a thick extracellular matrix, mimicking early steps of mitral valve remodelling. Lesions were prevented by 5-HT2A or 5-HT2B receptor antagonists and in transgenic Htr2B -/- or Htr2A/2B -/- mice. Surprisingly, valve lesions were mainly formed by numerous non-proliferative CD34+ endothelial progenitors. These progenitors originated from bone marrow (BM) as revealed by BM transplantation. The initial steps of mitral valve remodelling involved mobilization of BM-derived CD34+ CD31+ cells by 5-HT2B receptor stimulation. Analysis of human prolapsed mitral valves showing spontaneous degenerative lesions, demonstrated the presence of non-proliferating CD34+ /CD309+ /NOS3+ endothelial progenitors expressing 5-HT2B receptors. CONCLUSIONS AND IMPLICATIONS: BM-derived endothelial progenitor cells make a crucial contribution to the remodelling of mitral valve tissue. Our data describe a new and important mechanism underlying human VHD.


Asunto(s)
Células Progenitoras Endoteliales , Enfermedades de las Válvulas Cardíacas/metabolismo , Válvula Mitral/metabolismo , Receptor de Serotonina 5-HT2B/metabolismo , Animales , Trasplante de Médula Ósea , Células Progenitoras Endoteliales/metabolismo , Enfermedades de las Válvulas Cardíacas/patología , Masculino , Ratones Transgénicos , Válvula Mitral/efectos de los fármacos , Válvula Mitral/patología , Norfenfluramina/farmacología , Receptor de Serotonina 5-HT2A/genética , Receptor de Serotonina 5-HT2B/genética , Antagonistas del Receptor de Serotonina 5-HT2/farmacología
19.
Ann Thorac Surg ; 103(1): 92-97, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27577036

RESUMEN

BACKGROUND: This study was conducted to identify preoperative predictors of postoperative atrial fibrillation (POAF) after isolated coronary artery bypass grafting (CABG) by using a Bayesian analysis that included information from prior studies. METHODS: We performed a prospective observational study from October 2008 to December 2013 of 1,481 patients who underwent isolated CABG with cardiopulmonary bypass and had no history of AF. Bayesian analysis was used to study the preoperative risks factors for POAF. RESULTS: The POAF incidence was 21%. Multivariate analysis identified the following independent predictors of POAF after CABG: high CHA2DS2-VASc (Congestive heart failure, Hypertension [blood pressure >140/90 mm Hg or treated hypertension on medication], Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, vascular disease, Age 65 to 74 years, Sex category [female sex]) score (odds ratio [OR], 1.23; 95% credible interval [CI], 1.14 to 1.33 per 1-point increment, probability (Pr) [OR > 1] = 1), severe obesity with a body mass index of 35 kg/m2 or higher (OR, 1.28; 95% CI, 1.12 to 1.45; Pr [OR > 1] = 1), preoperative ß-blocker use (OR, 1.12; 95% CI, 1.06 to 1.20; Pr [OR > 1] = 1), preoperative antiplatelet therapy (OR, 1.75; 95% CI, 1.14 to 2.79, Pr [OR > 1] = 1), and renal insufficiency with a creatinine clearance of less than 60 mL/min (OR, 1.34; 95% CI, 1.03 to 1.74; Pr [OR > 1] = 1). CONCLUSIONS: This prospective Bayesian analysis identified five independent preoperative predictors of POAF after isolated CABG with cardiopulmonary bypass: CHA2DS2-VASc score, severe obesity, preoperative ß-blocker use, preoperative antiplatelet therapy, and renal failure. The main interest in the CHA2DS2-VASc score as a predictor of POAF is that it is a simple and widely used bedside tool. Patients with these independent predictors of POAF may constitute a target population to test preventive strategies, such as non-antiarrhythmic and antiarrhythmic drugs.


Asunto(s)
Fibrilación Atrial/etiología , Teorema de Bayes , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Complicaciones Posoperatorias , Medición de Riesgo , Anciano , Fibrilación Atrial/epidemiología , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Factores de Riesgo
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