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1.
Medicine (Baltimore) ; 101(35): e30190, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107504

RESUMO

Early mortality post-ST-segment elevation myocardial infarction (STEMI) in France remains high. The multicentre France Percutaneous Coronary Intervention Registry includes every patient undergoing coronary angiography in France. We analyzed the prevalence and impact of unmodifiable and modifiable risk factors on 30-day survival in patients experiencing STEMI. Patients admitted for STEMI between 01/2014 and 12/2016 were included in the analysis. Patients with nonobstructive coronary artery disease, with cardiogenic shock or cardiac arrest without STEMI, were excluded. Prehospital, clinical and procedural data were collected prospectively by the cardiologist in the cath lab using medical reporting software. Information on outcomes, including mortality, was obtained by a dedicated research technician by phone calls or from medical records. Marginal Cox proportional hazards regression was used to test the predictive value for survival at 30 days in a multivariable analysis. Included were 2590 patients (74% men) aged 63 ± 14 years. During the first month, 174 patients (6.7%) died. After adjustment, unmodifiable variables significantly associated with reduced 30-day survival were: age > 80 years (prevalence 15%; hazard ratio [HR] 2.7; 95% confidence interval [CI] 1.5-4.7), chronic kidney disease (2%; HR 5.3; 95% CI 2.6-11.1), diabetes mellitus (14%; HR 1.6; 95% CI 1.0-2.5), anterior or circumferential electrical localization (39%; HR 2.0; 95% CI 1.4-2.9), and Killip class 2, 3, or 4 (7%; HR 3.4; 95% CI 1.9-5.9; 2%; HR 10.1; 95% CI 5.3-19.4; 4%; HR 18; 95% CI 10.8-29.8, respectively). Among modifiable variables, total ischemic time > 3 hours (68%; HR 1.8; 95% CI 1.1-3.0), lack of appropriate premedication (18%; HR 2.2; 95% CI 1.5-3.3), and post-PCI TIMI < 3 (6%; HR 4.9; 95% CI 3.2-7.6) were significantly associated with reduced 30-day survival. Most predictors of 30-day survival post-STEMI are unmodifiable, but outcomes might be improved by optimizing modifiable factors, most importantly ischemic time and appropriate premedication.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , França/epidemiologia , Humanos , Masculino , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Sistema de Registros
2.
Arch Cardiovasc Dis ; 115(8-9): 467-475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35872078

RESUMO

BACKGROUND: On 26 September 2019, an industrial fire occurred in the Lubrizol factory in Rouen (France), exposing the population to the inhalation of many volatile toxic agents secondary to combustion. AIM: To assess the impact of the Lubrizol factory fire on the incidence of coronary artery events. METHODS: All coronary angiograms performed in Rouen (exposed) and Le Havre (unexposed) from May 2019 to December 2019 were extracted from the prospective France Percutaneous Coronary Intervention (France PCI) registry. To study the impact of the fire on coronary events, an interrupted time series analysis was performed in Rouen, with adjustment on Le Havre in an autoregressive moving average (ARMA)(1,1) model with the precision of 1 week. The primary outcome was the incidence of acute coronary syndrome, and the secondary outcome was the incidence of ST-segment elevation myocardial infarction. RESULTS: The mean number of acute coronary syndromes per week in the exposed zone (Rouen) increased non-significantly from 37.5±9.4 before the fire to 43.2±6.2 after the fire, for an estimated effect of +5.5 (95% confidence interval -0.7 to 11.8; P=0.09) events per week. In municipalities exposed to the plume of smoke (subgroup of Rouen), the mean number of acute coronary syndromes increased non-significantly from 7.3±2.8 before the fire to 8.7±3.6 after the fire, for an estimated effect of +1.0 (95% confidence interval -2.0 to 4.0; P=0.51) events per week. The results were similar when taking into account only ST-segment elevation myocardial infarctions or all coronary events. CONCLUSIONS: Our study did not find a significant effect of the Lubrizol factory fire on the incidence of acute coronary syndrome. Further studies are needed to investigate the impact of industrial accidents on air pollution and coronary events.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
3.
J Am Coll Cardiol ; 78(19): 1875-1885, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34736563

RESUMO

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana , Estenose Coronária , Vasos Coronários , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/mortalidade , Idoso , Angiografia Coronária/métodos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/etiologia , Estenose Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Efeitos Adversos de Longa Duração/mortalidade , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Valor Preditivo dos Testes , Medição de Risco/métodos , Índice de Gravidade de Doença
4.
J Am Coll Emerg Physicians Open ; 1(6): 1168-1176, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33363285

RESUMO

Objectives: The aim of this study was to assess the impact of the coronavirus disease 2019 (COVID-19) outbreak on incidence, delays, and outcomes of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) in France. Methods: We analyzed all patients undergoing PPCI <24 hours STEMI included in the prospective France PCI registry. The 2 groups were compared on mean monthly number of patients, delays in the pathway care, and in-hospital major adverse cardiac events (MACE: death, stent thrombosis, myocardial infarction, unplanned coronary revascularization, stroke, and major bleeding). Results: From January 15, 2019 to April 14, 2020, 2064 STEMI patients undergoing PPCI were included: 1942 in the prelockdown group and 122 in the lockdown group. Only 2 cases in the lockdown group were positive for COVID-19. A significant drop (12%) in mean number of STEMI/month was observed in the lockdown group compared with prelockdown (139 vs 122, P < 0.04). A significant increase in "symptom onset to first medical contact" delay was found for patients who presented directly to the emergency department (ED) (238 minutes vs 450 minutes; P = 0.04). There were higher rates of in-hospital MACE (7.7% vs 12.3%; P = 0.06) and mortality (4.9% vs 8.2%; P = 0.11) in the lockdown group but the differences were not significant. Conclusion: According to the multicenter France PCI registry, the COVID-19 outbreak in France was associated with a significant decline in STEMI undergoing PPCI and longer transfer time for patients who presented directly to the ED. Mortality rates doubled, but the difference was not statistically significant.

5.
BMC Cardiovasc Disord ; 18(1): 193, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340532

RESUMO

BACKGROUND: Experimental studies suggest that morphine may protect the myocardium against ischemia-reperfusion injury by activating salvage kinase pathways. The objective of this two-center, randomized, double-blind, controlled trial was to assess potential cardioprotective effects of intra-coronary morphine in patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous intervention. METHODS: Ninety-one patients with STEMI were randomly assigned to intracoronary morphine (1 mg) or placebo at reperfusion of the culprit coronary artery. The primary endpoint was infarct size/left ventricular mass ratio assessed by magnetic resonance imaging on day 3-5. Secondary endpoints included the areas under the curve (AUC) for troponin T and creatine kinase over three days, left ventricular ejection fraction assessed by echocardiography on days 1 and 6, and clinical outcomes. RESULTS: Infarct size/left ventricular mass ratio was not significantly reduced by intracoronary morphine compared to placebo (27.2% ± 15.0% vs. 30.5% ± 10.6%, respectively, p = 0.28). Troponin T and creatine kinase AUCs were similar in the two groups. Morphine did not improve left ventricular ejection fraction on day 1 (49.7 ± 10.3% vs. 49.3 ± 9.3% with placebo, p = 0.84) or day 6 (48.5 ± 10.2% vs. 49.0 ± 8.5% with placebo, p = 0.86). The number of major adverse cardiac events, including stent thrombosis, during the one-year follow-up was similar in the two groups. CONCLUSIONS: Intracoronary morphine at reperfusion did not significantly reduce infarct size or improve left ventricular systolic function in patients with STEMI. Presence of comorbidities in some patients may contribute to explain these results. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01186445 (date of registration: August 23, 2010).


Assuntos
Morfina/administração & dosagem , Intervenção Coronária Percutânea , Substâncias Protetoras/administração & dosagem , Idoso , Método Duplo-Cego , Feminino , França , Humanos , Injeções Intra-Arteriais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Morfina/efeitos adversos , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Intervenção Coronária Percutânea/efeitos adversos , Substâncias Protetoras/efeitos adversos , Recuperação de Função Fisiológica , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
6.
Stem Cells ; 32(1): 216-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24115309

RESUMO

Mesenchymal stem cells (MSC) are known to repair broken heart tissues primarily through a paracrine fashion while emerging evidence indicate that MSC can communicate with cardiomyocytes (CM) through tunneling nanotubes (TNT). Nevertheless, no link has been so far established between these two processes. Here, we addressed whether cell-to-cell communication processes between MSC and suffering cardiomyocytes and more particularly those involving TNT control the MSC paracrine regenerative function. In the attempt to mimic in vitro an injured heart microenvironment, we developed a species mismatch coculture system consisting of terminally differentiated CM from mouse in a distressed state and human multipotent adipose derived stem cells (hMADS). In this setting, we found that crosstalk between hMADS and CM through TNT altered the secretion by hMADS of cardioprotective soluble factors such as VEGF, HGF, SDF-1α, and MCP-3 and thereby maximized the capacity of stem cells to promote angiogenesis and chemotaxis of bone marrow multipotent cells. Additionally, engraftment experiments into mouse infarcted hearts revealed that in vitro preconditioning of hMADS with cardiomyocytes increased the cell therapy efficacy of naïve stem cells. In particular, in comparison with hearts treated with stem cells alone, those treated with cocultured ones exhibited greater cardiac function recovery associated with higher angiogenesis and homing of bone marrow progenitor cells at the infarction site. In conclusion, our findings established the first relationship between the paracrine regenerative action of MSC and the nanotubular crosstalk with CM and emphasize that ex vivo manipulation of these communication processes might be of interest for optimizing current cardiac cell therapies.


Assuntos
Compartimento Celular/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Miócitos Cardíacos/metabolismo , Nanotubos , Animais , Técnicas de Cocultura , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Comunicação Parácrina
7.
Am J Cardiol ; 112(10): 1619-24, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24012031

RESUMO

The ratio of early transmitral blood flow velocity over tissue Doppler early diastolic mitral annulus velocity (E/e') was found unreliable for estimating pulmonary capillary wedge pressure (PCWP) in patients with decompensated systolic heart failure (HF). The objective of this study was to test its reliability in stable HF. Therefore, 130 consecutive patients with a left ventricular (LV) ejection fraction of <35% and stable HF underwent right-sided cardiac catheterization and transthoracic echocardiography with measurement of transmitral flow velocities (E, A) and mitral annulus velocities during systole (s') and diastole (e'). Mean age was 56 ± 11 years and mean LV ejection fraction was 28 ± 8%; 48% had PCWP of >15 mm Hg. E/e'septal correlated more strongly with PCWP (r = 0.53) compared with E/e'lateral (r = 0.41) and E/e'mean (r = 0.50; all p values <0.001). The area under the receiver operating characteristic curve (AUC) of E/e' ratios for PCWP estimation was 0.79 (95% confidence interval [CI] 0.70 to 0.87) for E/e'septal, 0.72 (95% CI 0.63 to 0.82) for E/elateral, and 0.79 (95% CI 0.70 to 0.87) for E/emean (all p values <0.0001). AUCs of E/eseptal and E/emean did not vary with s'septal, QRS width, or resynchronization. Using a cutoff of 8, negative predictive value of E/e'septal was 89% and negative likelihood ratio of 0.15. E/e'lateral showed good diagnostic performance only in patients with s'lateral of >4.5 cm/s (n = 77, 59%; AUC = 0.82; 95% CI 0.71 to 0.92; s'lateral of ≤4.5 cm/s: AUC = 0.54; 95% CI 0.38 to 0.70; p = 0.005). In conclusion, e' is useful for estimating LV filling pressure in stable severe systolic HF. E/e'septal showed good diagnostic performance for detecting normal filling pressures.


Assuntos
Ecocardiografia Doppler/métodos , Insuficiência Cardíaca Sistólica/fisiopatologia , Função Ventricular Esquerda , Pressão Ventricular/fisiologia , Cateterismo Cardíaco , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Volume Sistólico
8.
Int J Cardiol ; 168(2): 1056-61, 2013 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-23159410

RESUMO

BACKGROUND: There is growing evidence that transradial (TRI) as compared to transfemoral (TFI) percutaneous coronary intervention (PCI) is associated with improved clinical outcome driven by less hemorrhagic complications, in particular in STEMI patients receiving aggressive antithrombotic treatment. Feasibility rate of TRI in STEMI patients has not yet been evaluated. METHODS/RESULTS: Four-hundred seventy-five consecutive STEMI patients (<12h) without cardiogenic shock were prospectively screened for this all-comer single-centre registry between January 2008 and August 2010. Nine patients were excluded for a priori ineligibility for TRI (forearm shunt for dialysis, prior TRI failure). In the 466 patients enrolled, the operator's opinion about ease of radial puncture was assessed in 4 categories, based on radial pulse quality. Operators were advised not to attempt TRI if ease of puncture was judged "probably difficult/impossible". In case of puncture failure the operator switched immediately to TFI. The mean age of patients was 61 ± 14 (range 27-94) years. Seventy-three percent were men, 17% had diabetes. Nine percent had previous PCI. Glycoprotein inhibitors were used in 70%, and thrombectomy was performed in 70% of patients. PCI was performed using 6F and 5F guiding catheters. Procedural success rate was 98.2% (TIMI flow ≥ 2). In 4.1% (n=19) of patients the operator judged ease of radial puncture "probably difficult/impossible" and no TRI attempt was performed (primary TFI). In the 447 patients with TRI attempt, TRI failure requiring switch to TFI (secondary TFI) was necessary in 22 patients (4.7% of total) following radial puncture failure (n=15), dissection of the radial artery (n=1), prohibitive tortuosities or stenosis of the upper limb axis (n=2), or non-selective position or lack of stability of the guiding catheter (n=2). After the start of the angioplasty procedure, switch from TR to TF was not necessary in any patient. In total, the overall feasibility rate of TRI was 91.2%. Independent predictors of final TFI were age ≥ 80 years (adjusted OR: 2.37; 95% CI:1.05-5.34, p=0.037), body weight<60 kg (adjusted OR: 2.84; 95% CI:1.22-6.59, p=0.015); and previous PCI (adjusted OR: 3.42; 95% CI:1.40-8.37, p=0.007); female gender was borderline significant (adjusted OR:2.10; 95% CI:0.97-4.54, p=0.059). CONCLUSION: In STEMI patients without cardiogenic shock and without a priori indication for TFI, PCI can be performed via the radial artery in more than 90% of cases with high procedural success rate. Operator's judgement of eligibility for TRI based on radial pulse quality is predictive of successful TRI in 95% of cases. TR failure is significantly more common in the elderly and in patients with low body weight.


Assuntos
Cateterismo Cardíaco/métodos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/métodos , Artéria Radial/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros
9.
Catheter Cardiovasc Interv ; 81(1): 15-23, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22744871

RESUMO

OBJECTIVES: The aim of this prospective, multicenter study was to assess the safety, feasibility, acceptance, and cost of ambulatory transradial percutaneous coronary intervention (PCI) under the conditions of everyday practice. BACKGROUND: Major advances in PCI techniques have considerably reduced the incidence of post-procedure complications. However, overnight admission still constitutes the standard of care in most interventional cardiology centers. METHODS: Eligibility for ambulatory management was assessed in 370 patients with stable angina referred to three high-volume angioplasty centers. On the basis of pre-specified clinical and PCI-linked criteria, 220 patients were selected for ambulatory PCI. RESULTS: The study population included a substantial proportion of patients with complex procedures: 115 (52.3%) patients with multivessel coronary artery disease, 50 (22.7%) patients with multilesion procedures, and 60 (21.5%) bifurcation lesions. After 4-6 hr observation period, 213 of the 220 patients (96.8%) were cleared for discharge. The remaining seven (3.2%) patients were kept overnight for unstable angina (n = 1), atypical chest discomfort (n = 2), puncture site hematoma (n = 1), or non-cardiovascular reasons (n = 3). Within 24 hr after discharge, no patients experienced readmission, stent occlusion, recurrent ischemia, or local complications. Furthermore, 99% of patients were satisfied with ambulatory management and 85% reported no anxiety. The average non-procedural cost was lower for ambulatory PCI than conventional PCI (1,230 ± 98 Euros vs. 2,304 ± 1814 Euros, P < 10(-6)). CONCLUSIONS: Ambulatory PCI in patients with stable coronary artery disease is safe, effective, and well accepted by the patients. It may both significantly reduce costs and optimize hospital resource utilization.


Assuntos
Assistência Ambulatorial/economia , Assistência Ambulatorial/métodos , Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/terapia , Redução de Custos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Estável/diagnóstico por imagem , Angina Estável/terapia , Angioplastia Coronária com Balão/economia , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Análise Custo-Benefício , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/terapia , Alta do Paciente/economia , Alta do Paciente/tendências , Estudos Prospectivos , Artéria Radial , Stents , Fatores de Tempo , Resultado do Tratamento
10.
PLoS One ; 7(10): e46698, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23056408

RESUMO

Transplantation of muscle precursor cells is of therapeutic interest for focal skeletal muscular diseases. However, major limitations of cell transplantation are the poor survival, expansion and migration of the injected cells. The massive and early death of transplanted myoblasts is not fully understood although several mechanisms have been suggested. Various attempts have been made to improve their survival or migration. Taking into account that muscle regeneration is associated with the presence of macrophages, which are helpful in repairing the muscle by both cleansing the debris and deliver trophic cues to myoblasts in a sequential way, we attempted in the present work to improve myoblast transplantation by coinjecting macrophages. The present data showed that in the 5 days following the transplantation, macrophages efficiently improved: i) myoblast survival by limiting their massive death, ii) myoblast expansion within the tissue and iii) myoblast migration in the dystrophic muscle. This was confirmed by in vitro analyses showing that macrophages stimulated myoblast adhesion and migration. As a result, myoblast contribution to regenerating host myofibres was increased by macrophages one month after transplantation. Altogether, these data demonstrate that macrophages are beneficial during the early steps of myoblast transplantation into skeletal muscle, showing that coinjecting these stromal cells may be used as a helper to improve the efficiency of parenchymal cell engraftment.


Assuntos
Macrófagos/citologia , Músculo Esquelético/citologia , Distrofias Musculares/terapia , Mioblastos/citologia , Animais , Western Blotting , Movimento Celular/fisiologia , Proliferação de Células , Sobrevivência Celular/fisiologia , Células Cultivadas , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
J Sex Med ; 9(11): 2827-37, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22908904

RESUMO

INTRODUCTION: Animal models of urinary incontinence and erectile dysfunction following radical prostatectomy (RP) are lacking. AIMS: To develop an animal model of combined post-RP urethral sphincter and erectile dysfunctions, and noninvasive methods to assess erectile function (EF) and urinary sphincter function (USF) during prolonged follow-up. METHODS: In the main experiments, 60 male Sprague Dawley rats were randomized to a sham operation (N = 30) or electrocautery of both sides of the striated urethral sphincter (N = 30). EF and USF were evaluated preoperatively and on postoperative days 7, 15, 30, 60, and 90. Sphincter and penile tissue samples were evaluated histologically on days 7 (N = 10) and 30 (N = 10) to detect apoptosis (TUNEL assays) and fibrosis (Trichrome Masson staining). MAIN OUTCOME MEASURES: To assess EF, we measured systemic and penile blood flow using penile laser Doppler and penile rigidity using a durometer before and after apomorphine injection. USF was assessed based on the retrograde leak point pressure (LPPr). RESULTS: Apomorphine increased baseline Doppler flow by 180% (95% confidence interval, 156-202%) and penile hardness from 3.49 ± 0.5 to 7.16 ± 0.82 Shore A units but did not change systemic arterial flow. Mean LPPr was 76.8 ± 6.18 mm Hg at baseline and decreased by 50% after injury, with no response to apomorphine on day 7. EF and USF impairments persisted up to 90 days post injury. Histology showed penile apoptosis on day 7 and extensive urethral sphincter and penile fibrosis on day 30. Our data did not allow us to determine whether the impairment in erectile response to apomorphine preponderantly reflected arterial penile insufficiency or veno-occlusive dysfunction. CONCLUSION: Electrocautery of the striated urethral sphincter caused severe and lasting impairment of EF and USF that could be monitored repeatedly using minimally invasive methods. This new animal model may hold potential for developing new treatments designed to correct post-RP impairments.


Assuntos
Modelos Animais de Doenças , Impotência Vasculogênica/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Prostatectomia , Uretra/fisiopatologia , Incontinência Urinária/fisiopatologia , Animais , Apoptose/fisiologia , Seguimentos , Masculino , Ereção Peniana/fisiologia , Ratos , Ratos Sprague-Dawley , Urodinâmica/fisiologia
12.
Pulm Circ ; 1(3): 377-82, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22140627

RESUMO

To evaluate the vasoconstrictor component of PH in CHF by investigating the hemodynamic response to inhaled nitric oxide (iNO) and to determine whether this response was influenced by the phosphodiesterase 5 gene (PDE5) G(1142)T polymorphism. CHF patients underwent right heart catheterization at rest and after 20 ppm of iNO and plasma cGMP and PDE5 G(1142)T polymorphism determinations. Of the 72 included CHF patients (mean age, 53±1 years; mean left ventricular ejection fraction, 29±1%; and mean pulmonary artery pressure, 25.5±1.3 mmHg), 54% had ischemic heart disease. Proportions of patients with the TT, GT, and GG genotypes were 39%, 42% and 19% respectively. Baseline hemodynamic characteristics were not significantly different across PDE5 genotype groups, although pulmonary capillary wedge pressure (PCWP) tended to be lower in the TT group (P=0.09). Baseline plasma cGMP levels were significantly lower in the TT than in the GG and GT patients. With iNO, PVR diminished in TT (-33%) but not GG (-1.6%) or GT (0%) patients (P=0.002); and PCWP increased more in TT than in GT (P<0.05) or GG (P<0.003) patients. The PDE5 G(-1142) polymorphism is therefore a major contributor to the iNO-induced PVR decrease in CHF.

14.
Br J Clin Pharmacol ; 71(6): 844-51, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21564160

RESUMO

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A(2) and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease. WHAT THIS STUDY ADDS: • This randomized, double-blind, placebo-controlled trial demonstrates that repeated-dose terutroban for 15 days improves endothelial function and inhibits thromboxane A(2) -induced platelet aggregation in high-cardiovascular-risk patients taking 300 mg of aspirin per day. Terutroban may prove useful for preventing cardiovascular events in such patients. AIMS: The specific TP receptor antagonist terutroban improves endothelial function after a single dose in patients with coronary artery disease. Our aim was to evaluate the effects and dose dependency of repeated-dose terutroban on endothelial function and platelet aggregation in high-cardiovascular-risk patients with carotid atherosclerosis. METHODS: We randomly allocated 48 patients taking 300 mg aspirin per day to placebo or to one of three terutroban dosages (2.5, 5 or 10 mg) for 15 days in a double-blind study. Flow-mediated vasodilatation was evaluated before and 2 h after the first oral dose on day 0 and 2 h after the last oral dose on day 14. RESULTS: On day 0 and day 14, all three terutroban dosages improved flow-mediated vasodilatation and abolished platelet aggregation induced by the TP receptor agonist U46619, without changing the aggregation response to ADP or collagen. CONCLUSION: Terutroban, by chronically improving endothelium-dependent vasodilatation and inhibiting platelet aggregation, may prove useful for preventing cardiovascular events in high-risk patients.


Assuntos
Aterosclerose/tratamento farmacológico , Doença da Artéria Coronariana/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Naftalenos/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Propionatos/administração & dosagem , Receptores de Tromboxanos/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Propionatos/uso terapêutico , Receptores de Tromboxanos/administração & dosagem , Resultado do Tratamento
15.
Stem Cells ; 29(5): 812-24, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21433223

RESUMO

Because stem cells are often found to improve repair tissue including heart without evidence of engraftment or differentiation, mechanisms underlying wound healing are still elusive. Several studies have reported that stem cells can fuse with cardiomyocytes either by permanent or partial cell fusion processes. However, the respective physiological impact of these two processes remains unknown in part because of the lack of knowledge of the resulting hybrid cells. To further characterize cell fusion, we cocultured mouse fully differentiated cardiomyocytes with human multipotent adipose-derived stem (hMADS) cells as a model of adult stem cells. We found that heterologous cell fusion promoted cardiomyocyte reprogramming back to a progenitor-like state. The resulting hybrid cells expressed early cardiac commitment and proliferation markers such as GATA-4, myocyte enhancer factor 2C, Nkx2.5, and Ki67 and exhibited a mouse genotype. Interestingly, human bone marrow-derived stem cells shared similar reprogramming properties than hMADS cells but not human fibroblasts, which suggests that these features might be common to multipotent cells. Furthermore, cardiac hybrid cells were preferentially generated by partial rather than permanent cell fusion and that intercellular structures composed of f-actin and microtubule filaments were involved in the process. Finally, we showed that stem cell mitochondria were transferred into cardiomyocytes, persisted in hybrids and were required for somatic cell reprogramming. In conclusion, by providing new insights into previously reported cell fusion processes, our data might contribute to a better understanding of stem cell-mediated regenerative mechanisms and thus, the development of more efficient stem cell-based heart therapies.


Assuntos
Fusão Celular , Células-Tronco Mesenquimais/citologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/citologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Células Cultivadas , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
EuroIntervention ; 4(1): 93-8, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-19112785

RESUMO

AIMS: The aim of this study was to determine the impact of bifurcation lesions on outcomes after primary percutaneous intervention (PCI) for acute myocardial infarction. METHODS AND RESULTS: We retrospectively reviewed a single-centre database of 646 patients admitted for primary angioplasty within 12 hours after AMI. We compared baseline characteristics and outcomes between bifurcation and non-bifurcation lesions. Bifurcation lesions were found in 23% of patients. They predominantly involved the left anterior descending artery. Provisional T-stenting was used in 89.3% of patients (with stenting of the main branch in 82% and of both branches in 7.3%), side-branch protection in 54.6%, and final kissing balloon inflation in 33%. The procedural success rate was 92% for the main branch of bifurcation lesions compared with 93% for non-bifurcation lesions (P=0.65). Major adverse cardiac event (MACE) rates were comparable in the two groups: in-hospital MACE was 13.3% in the bifurcation group versus 11.4% in the non-bifurcation group (P=0.72), and the 1-year total MACE rate was 22.6% in the bifurcation group versus 19.5% in the non-bifurcation group (P=0.56). CONCLUSIONS: Bifurcation lesions are common in patients with AMI. In a population with AMI, immediate and mid-term outcomes of primary PCI were similar in patients with and without bifurcation lesions.


Assuntos
Angioplastia Coronária com Balão , Vasos Coronários/patologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
18.
Circulation ; 115(11): 1354-62, 2007 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-17353440

RESUMO

BACKGROUND: The outcome of resuscitated patients after cardiac arrest complicating acute myocardial infarction remains poor, primarily because of the relatively low success rates of cardiopulmonary resuscitation management. Existing data suggest potential beneficial effects of early myocardial reperfusion, but the predictors of survival in these patients remain unknown. METHODS AND RESULTS: From 1995 to 2005, 186 patients (78% men; mean age, 60.4+/-13.8 years) underwent immediate percutaneous coronary intervention after successful resuscitation for cardiac arrest complicating acute myocardial infarction. Prompt prehospital management was performed by mobile medical care units in 154 of 186 patients, whereas 32 had in-hospital cardiac arrest. Infarct location was anterior in 105 patients (56%), and shock was present on admission in 96 (52%). Percutaneous coronary intervention (stenting rate 90%) was successful in 161 of 186 patients (87%). Six-month survival rate was 100 of 186 (54%), and 6-month survival free of neurological sequelae was 46%. By multivariate analysis, predictors of 6-month survival were a shorter interval between the onset of cardiac arrest and arrival of a first responder (odds ratio, 0.67; 95% CI, 0.54 to 0.84), a shorter interval between the onset of cardiac arrest and return of spontaneous circulation (odds ratio, 0.91; 95% CI, 0.87 to 0.96), and absence of diabetes (odds ratio, 7.30; 95% CI, 1.80 to 29.41). CONCLUSIONS: In patients with resuscitated cardiac arrest complicating acute myocardial infarction, prompt prehospital management and early revascularization were associated with a 54% survival rate at 6 months. A strategy including adequate prehospital management, early revascularization, and specific care in dedicated intensive care units should be strongly considered in resuscitated patients after cardiac arrest complicating acute myocardial infarction.


Assuntos
Angioplastia Coronária com Balão/mortalidade , Reanimação Cardiopulmonar/mortalidade , Serviços Médicos de Emergência/estatística & dados numéricos , Parada Cardíaca/mortalidade , Infarto do Miocárdio/mortalidade , Idoso , Angioplastia Coronária com Balão/estatística & dados numéricos , Cateterismo Cardíaco/mortalidade , Cateterismo Cardíaco/estatística & dados numéricos , Reanimação Cardiopulmonar/estatística & dados numéricos , Cuidados Críticos/estatística & dados numéricos , Eletrocardiografia , Serviços Médicos de Emergência/métodos , Feminino , Seguimentos , Parada Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Circulation ; 110(11): 1473-6, 2004 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-15226213

RESUMO

BACKGROUND: The newly developed percutaneous heart valve (PHV) implantation technique decreases transaortic pressure gradient in patients with aortic stenosis. PHV replacement effects on left ventricular (LV) global and regional systolic function are currently unknown. METHODS AND RESULTS: Eight patients with severe aortic stenosis had 2D echocardiography at baseline and 24 hours after PHV implantation to evaluate changes in LV volume and LV ejection fraction. Regional function, ie, both peak systolic anterior and posterior wall tissue velocity, as well as strain and strain rate imaging, were measured by tissue Doppler imaging from a short-axis view. At 24 hours, a significant reduction in transaortic mean pressure gradient (from 46+/-15 to 8+/-3 mm Hg; P<0.0001) was accompanied by an increase in aortic valve area (from 0.59+/-0.11 to 1.69+/-0.11 cm2; P<0.0001). LV end-diastolic volume remained unchanged (102+/-36 to 101+/-12 mL; P=NS), whereas LV ejection fraction increased (48+/-18% to 57+/-12%; P<0.01). Improvement in posterior wall displacement (posterior wall tissue velocity increased from 2.2+/-0.5 to 4.4+/-1.0 cm/s(-1); P=0.0003) and deformation (strain rate imaging increased from 1.0+/-0.3 to 1.9+/-0.7 s(-1), P=0.009, and strain increased from 11+/-5% to 17+/-9%; P=0.02) were observed. CONCLUSIONS: Immediately after PHV replacement, improvement of LV global and regional systolic function was evidenced by tissue Doppler imaging.


Assuntos
Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Sístole , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia Doppler em Cores , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Período Pós-Operatório , Choque Cardiogênico/etiologia , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/cirurgia
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