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BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.
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Injúria Renal Aguda , Insuficiência Renal Crônica , Humanos , Angiografia Coronária/efeitos adversos , Solução Salina , Resultado do Tratamento , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/prevenção & controle , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnósticoRESUMO
Macrophages play a vital role in cardiac repair following myocardial infarction (MI). An enriched environment (EE) is involved in the regulation of macrophage-related activities and disease progression; however, whether EE affects the phenotype and function of macrophages to improve postinfarction cardiac repair remains unknown. In this study, we found that EE improved cardiac function, decreased mortality, and ameliorated adverse ventricular remodeling in mice after MI, with these outcomes closely related to the increased survival of Ly6Clow macrophages and their CCR2-MHCIIlow subsets. EE increased the expression of brain-derived neurotrophic factor (BDNF) in the hypothalamus, leading to higher circulating levels of BDNF, which, in turn, regulated the cardiac macrophages. BDNF bound to tropomyosin receptor kinase B to activate downstream ERK1/2 and AKT pathways, promoting macrophage survival. These findings demonstrate that EE optimizes postinfarction cardiac repair and highlights the significance of EE as a previously unidentified strategy for impeding adverse ventricular remodeling.
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Infarto do Miocárdio , Remodelação Ventricular , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Coração , Macrófagos/metabolismo , Camundongos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapia , Miocárdio/metabolismoRESUMO
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important and major player in the pathophysiology of hypercholesterolemia and atherosclerosis. Recently, PCSK9 has been implicated in the pathogenesis of inflammatory diseases. Whether PCSK9 is involved in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to investigate the relationship between PCSK9 and IPAH. Serum PCSK9, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß), and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay. Transthoracic echocardiography was performed among 40 IPAH patients and 20 control subjects. Hemodynamic data were collected via right heart catheterization in patients with IPAH. Serum PCSK9, TNF-α, IL-6, IL-1ß, and MCP-1 levels were significantly higher in IPAH patients than in control subjects (p < 0.001). Among enrolled IPAH patients, PCSK9 levels were higher in WHO-FC III/IV patients compared with those in WHO-FC I/II (p < 0.05), and were positively correlated with TNF-α, IL-6, MCP-1, N-Terminal pro-brain natriuretic peptide, pulmonary arterial systolic pressure (r = 0.653, p < 0.001), pulmonary arterial diastolic pressure (r = 0.466, p = 0.002), mean pulmonary arterial pressure (mPAP, r = 0.730, <0.001), pulmonary vascular resistance (r = 0.488, p = 0.001), and right ventricle diameter (r = 0.563, p < 0.001). In multiple regression analysis, mPAP was strongly associated with serum PCSK9 (ß = 0.694, p < 0.001), independent of other variables. Receiver operating characteristic curve analysis showed the optimal cutoff value of serum PCSK9 concentration for predicting IPAH was 90.67 ng/ml, with a sensitivity of 90.0% and a specificity of 85.0%. In conclusion, IPAH patients had elevated serum PCSK9 levels which correlated the presence and severity of pulmonary hypertension. PCSK9 may be a novel potential therapeutic target.
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BACKGROUND: H type hypertension is defined as homocysteine (Hcy) ≥ 10 µmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives. METHODS: We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected. RESULTS: In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 µmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension. CONCLUSIONS: The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.
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Genótipo , Homocisteína/sangue , Hipertensão/sangue , Hipertensão/epidemiologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiper-Homocisteinemia/complicações , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Ischaemic preconditioning elicited by brief periods of coronary occlusion and reperfusion protects the heart from a subsequent prolonged ischaemic insult. Here, we test the hypothesis that short-term non-ischaemic stimulation of hypertrophy renders the heart resistant to subsequent ischaemic injury. METHODS AND RESULTS: Transient transverse aortic constriction (TAC) was performed for 3 days in mice and then withdrawn for 4 days by aortic debanding, followed by subsequent exposure to myocardial ischaemia-reperfusion (I/R) injury. Following I/R injury, myocardial infarct size and apoptosis were significantly decreased, and cardiac dysfunction was markedly improved in the TAC preconditioning group compared with the control group. Mechanistically, TAC preconditioning markedly suppressed I/R-induced autophagy and preserved autophagic flux by deacetylating SOD2 via a SIRT3-dependent mechanism. Moreover, treatment with an adenovirus encoding SIRT3 partially mimicked the effects of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. Furthermore, in vivo lentiviral-mediated knockdown of Beclin 1 in the myocardium ameliorated the I/R-induced impairment of autophagic flux and was associated with a reduction in cell death, whereas treatment with a lentivirus encoding Beclin 1 abolished the cardioprotective effect of TAC preconditioning. CONCLUSIONS: The present study identifies TAC preconditioning as a novel strategy for induction of an endogenous self-defensive and cardioprotective mechanism against cardiac injury. Specifically, TAC preconditioning reduced myocardial autophagic cell death in a SIRT3/SOD2 pathway-dependent manner.
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Autofagia , Precondicionamento Isquêmico , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo , Animais , Apoptose , Proteína Beclina-1/antagonistas & inibidores , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Sirtuína 3/deficiência , Sirtuína 3/genéticaRESUMO
Brief episodes of ischaemia and reperfusion render the heart resistant to subsequent prolonged ischaemic insult, termed ischaemic preconditioning. Here, we hypothesized that transient non-ischaemic stress by hypertrophic stimulation would induce endogenous cardioprotective signalling and enhance cardiac resistance to subsequent ischaemic damage. Transient transverse aortic constriction (TAC) or Ang-â ¡ treatment was performed for 3-7 days in male mice and then withdrawn for several days by either aortic debanding or discontinuing Ang-â ¡ treatment, followed by subsequent exposure to regional myocardial ischaemia by in situ coronary artery ligation. Following ischaemia/reperfusion (I/R) injury, myocardial infarct size and apoptosis were markedly reduced and contractile function was significantly improved in the TAC preconditioning group compared with that in the control group. Similar results were observed in mice receiving Ang-â ¡ infusion. Mechanistically, TAC preconditioning enhanced ALDH2 activity, promoted AMPK activation and improved mitochondrial energy metabolism by increasing myocardial OXPHOS complex expression, elevating the mitochondrial ATP content and improving viable myocardium glucose uptake. Moreover, TAC preconditioning significantly mitigated I/R-induced myocardial iNOS/gp91phox activation, inhibited endoplasmic reticulum stress and ameliorated mitochondrial impairment. Using a pharmacological approach to inhibit AMPK signalling in the presence or absence of preconditioning, we demonstrated AMPK-dependent protective mechanisms of TAC preconditioning against I/R injury. Furthermore, treatment with adenovirus-encoded ALDH2 partially emulated the actions of hypertrophic preconditioning, as evidenced by improved mitochondrial metabolism, inhibited oxidative stress-induced mitochondrial damage and attenuated cell death through an AMPK-dependent mechanism, whereas genetic ablation of ALDH2 abrogated the aforementioned actions of TAC preconditioning. The present study demonstrates that preconditioning with hypertrophic stress protects the heart from I/R injury via mechanisms that improve mitochondrial metabolism, reduce oxidative/nitrative stress and inhibit apoptosis. ALDH2 is obligatorily required for the development of cardiac hypertrophic preconditioning and acts as the mediator of this process.
Assuntos
Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Aldeído-Desidrogenase Mitocondrial , Animais , Masculino , Camundongos , Mitocôndrias Cardíacas , MiocárdioRESUMO
The purpose of our study was to develop a simple clinical pre-procedure risk model based on clinical characteristics for the prediction of contrast-induced nephropathy (CIN) and major adverse cardiac events (MACEs) after percutaneous coronary intervention (PCI) in patients with diabetes. A total of 1113 patients with diabetes who underwent PCI with contrast exposure were randomized into a development group (n = 742) and a validation group (n = 371) in a 2:1 ratio. CIN was defined as an increase of either 25% or 0.5 mg/dL (44.2 µmol/L) in serum creatinine within 72 hours after contrast infusion. A simple CIN risk score based on independent predictors was established. Four variables were identified for our risk score model: LVEF < 40%, acute coronary syndrome (ACS), eGFR < 60, and contrast volume > 300 mL. Based on this new CIN risk score, the incidence of CIN had a significant trend with increased predicting score values of 5.9%, 32.9% and 60.0%, corresponding to low-, moderate- and high-risk groups, respectively. The novel risk assessment exhibited moderate discrimination ability for predicting CIN, with an AUC of 0.759 [95% CI 0.668-0.852, P = .001] in the validation cohort. It also had similar prognostic values for one-year follow-up MACE (C-statistic: 0.705 and 0.606 for new risk score and Mehran score, respectively). This novel risk prediction model could be effective for preventing nephropathy in diabetic patients receiving contrast media during surgical procedures.
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Síndrome Coronariana Aguda/terapia , Meios de Contraste/efeitos adversos , Doença da Artéria Coronariana/terapia , Técnicas de Apoio para a Decisão , Diabetes Mellitus , Nefropatias/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Bases de Dados Factuais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Incidência , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Distribuição Aleatória , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
BACKGROUND: Paraganglioma is a rare disease that can be lethal if undiagnosed. Thus, quick recognition is very important. Cardiac paragangliomas are found in patients who have hypertension. The classic symptoms are the triad of headaches, palpitations, and profuse sweating. We describe a very rare case of multiple paragangliomas of the heart and bilateral carotid artery without hypertension and outline the management strategies for this disease. CASE SUMMARY: A 46-year-old man presented with the chief complaint of recently recurrent chest pain with a history of hemangioma of the bilateral carotid artery that had been surgically removed. He was found to have an intracardiac mass in the right atrioventricular groove and underwent successful excision. The final pathology demonstrated that the intracardiac mass was a cardiac paraganglioma, and the patient had an increased level of normetanephrine in the blood. The pathology and immunohistochemistry results showed that the bilateral carotid masses were also paragangliomas. During the 3 mo follow-up period, the patient did not experience recurrence of chest pain. CONCLUSION: To our knowledge, this is the first case of multiple paragangliomas of the heart and neck without hypertension. This rare disease can be lethal if left undiagnosed. Thus, quick recognition is very important. The key to the diagnosis of cardiac paraganglioma is the presence of typical symptoms, including headaches, palpitations, profuse sweating, hypertension, and chest pain. Radiology can demonstrate the intracardiac mass. It is important to determine the levels of normetanephrine in the blood. The detection of genetic mutations is also recommended. Surgical resection is necessary to treat the disease and obtain pathological evidence.
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BACKGROUND: A percutaneous approach for pulmonary valve replacement (PVR) is a feasible alternative to surgical PVR in selected patients with severe pulmonary regurgitation after repair of tetralogy of Fallot. However, large right ventricular outflow tract (diameter ≥ 25 mm) remains challenging. METHODS: This retrospective multicenter study enrolled consecutive patients with large right ventricular outflow tract who underwent percutaneous PVR (Venus P-valve, Venus MedTech Inc, Hangzhou, China) (n = 35) or surgical PVR (homograft valve; n = 30) between May 2014 and April 2017. Patients were followed up at 1, 3, 6, and 12 months, and yearly thereafter. Main study outcomes were pulmonary valve function and right ventricular function at discharge and midterm follow-up. RESULTS: PVR was successful in all patients. Percutaneous compared with surgical PVR group had: similarly distributed baseline characteristics; shorter hospitalization, intensive care unit stay, and endotracheal intubation duration; lower cost; lower pulmonary valve gradient before discharge; lower pulmonary valve regurgitant grade (mean difference, -0.63; 95% CI -1.11 to -0.20, P = .022), pulmonary valve gradient (mean difference, -5.7 mm Hg; 95% CI -9.4 to -2.2 mm Hg, P = .005), and right ventricular end-diastolic volume index (mean difference, -9.5 mL/m2; 95% CI -16.9 to -3.1 mL/m2, P = .022); and greater right ventricular ejection fraction (mean difference, 5.4%; 95% CI 2.4%-8.3%, P = .002) at median 36 months follow-up, without deaths in either group. CONCLUSIONS: Percutaneous PVR using Venus P-valve appeared to be a safe, efficacious and minimally invasive alternative to surgical PVR in selected patients with large right ventricular outflow tract yielding better right ventricular and pulmonary valve function at midterm follow-up.
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Cateterismo Cardíaco/métodos , Implante de Prótese de Valva Cardíaca/métodos , Ventrículos do Coração/diagnóstico por imagem , Insuficiência da Valva Pulmonar/cirurgia , Valva Pulmonar/cirurgia , Volume Sistólico/fisiologia , Função Ventricular Direita/fisiologia , Adulto , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/diagnóstico , Insuficiência da Valva Pulmonar/fisiopatologia , Estudos RetrospectivosRESUMO
Quite a few studies have revealed the clinical values regarding the outcome predictions in the cohort of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and decision-making with the SYNTAX score. The Evaluation of Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left-Main Revascularization (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE) studies are the largest international randomized studies so far, comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in the treatment of left main coronary artery disease. Unfortunately, both studies failed to validate the value of the SYNTAX score in the selection of revascularization strategies for patients with coronary artery diseases (CAD).. This scenario prompted us to reconsider the inherent fallacies of the SYNTAX score in its derivation. We pointed out eight fallacies for the SYNTAX score in this paper. A recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score, available at http://www.catletscore.com, a novel angiographic scoring system, could be the remedies for the SYNTAX score.
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Angiografia Coronária/métodos , Ponte de Artéria Coronária , Doença da Artéria Coronariana , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Intervenção Coronária Percutânea , Projetos de Pesquisa/normas , Pesquisa Comparativa da Efetividade , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/classificação , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/patologia , Humanos , Seleção de Pacientes , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Reprodutibilidade dos TestesRESUMO
Although thrombelastography (TEG) has been widely implemented in the clinical setting of endovascular intervention, consensus on the optimal parameter for defining high ischemic risk patients is lacking due to the limited data about the relationship between various TEG parameters and clinical outcomes. In this article, we report a post hoc analysis of a prospective, single-center cohort study, including 447 patients with acute coronary syndrome (ACS). Arachidonic acid (AA)- or adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAAA or MAADP) was indicative of the net residual platelet reactivity after the treatment with aspirin or clopidogrel, respectively. AA% or ADP% was indices of the relative platelet inhibition rate on AA or ADP pathway. We found that each parameter alone was predictive of the risk of 6-month ischemic event, even after adjusting for confounding factors. However, the association between AA% and clinical outcome disappeared when further adjusted for MAAA. Likewise, inclusion of MAADP changed the significant relation between ADP% and clinical outcome. MAADP > 47.0 mm and MAAA > 15.1 mm were identified as the optimal cutoffs by receiver operating characteristic analysis. High MAAA (HR = 3.963; 95% CI: 1.152-13.632; P = 0.029) and high MAADP (HR = 5.185; 95% CI: 2.228-12.062; P < 0.001) were independent predictors when both were included in multivariable Cox regression hazards model. Interestingly, an even higher risk was found for the coexisting high MAAA and high MAADP (HR = 7.870; 95% CI: 3.462-17.899; P < 0.001). We conclude that when performing TEG to predict clinical efficacy, residual platelet reactivity has superiority over platelet inhibition rate as a measure of thrombotic risk in patients treated with aspirin and clopidogrel after ACS.
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Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Tromboelastografia , Difosfato de Adenosina/metabolismo , Idoso , Ácido Araquidônico/metabolismo , Aspirina/farmacologia , Plaquetas/metabolismo , Clopidogrel/farmacologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Remote ischemic preconditioning (RIPC) is one of the most powerful intrinsic cardioprotective strategies discovered so far and experimental data indicate that comorbidity may interfere with the protection by RIPC. Therefore, we investigate whether RIPC-induced cardioprotection was intact in hypercholesterolemic rat hearts exposed to ischemia reperfusion in vivo. Normal or hypercholesterolemic rat hearts were exposed to 30âmin of ischemia and 2âh of reperfusion, with or without RIPC, PI3K inhibitor wortmannin, MEK-ERK1/2 inhibitor PD98059, GSK3ß inhibitor SB216763. Infarct size, apoptosis, MG53, PI3K-p85, p-Akt, p-ERK1/2, p-GSK3ß, and cleaved Caspase-3 were determined. RIPC reduced infarct size, limited cardiomyocyte apoptosis following IR that was blocked by wortmannin but not PD98059. RIPC triggered unique cardioprotective signaling including MG53, phosphorylation of Akt, and glycogen synthase kinase-3ß (GSK3ß) in concert with reduced proapoptotic active caspase-3. In contrast, RIPC failed to reduce myocardial necrosis and apoptosis as well as to increase the phosphorylated Akt and GSK3ß in hypercholestorolemic myocardium. Importantly, we found that inhibition of GSK with SB216763 reduced myocardial infarct size in healthy and hypercholesterolemic hearts, but no additional cardioprotective effect was achieved when combined with RIPC. Our results suggest that acute GSK3ß inhibition may provide a novel therapeutic strategy for hypercholesterolemic patients during acute myocardial infarction, whereas RIPC is less effective due to signaling events that adversely affect GSK3ß.
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Hipercolesterolemia/complicações , Hipercolesterolemia/enzimologia , Precondicionamento Isquêmico , Fosfatidilinositol 3-Quinases/metabolismo , Androstadienos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , WortmaninaRESUMO
BACKGROUND: Coronary microembolization (CME) has been frequently seen in acute coronary syndromes and percutaneous coronary intervention. Small animal models are required for further studies of CME related to severe prognosis. This study aimed to explore a new mouse model of CME. METHODS: The mouse model of CME was established by injecting polystyrene microspheres into the left ventricular chamber during 15-s occlusion of the ascending aorta. Based on the average diameter and dosage used, 30 C57BL/6 male mice were randomly divided into five groups (n = 6 in each): 9 µm/500,000, 9 µm/800,000, 17 µm/200,000, 17 µm/500,000, and sham groups. The postoperative survival and performance of the mice were recorded. The mice were sacrificed 3 or 10 days after the surgery. The heart tissues were harvested for hematoxylin and eosin staining and Masson trichrome staining to compare the extent of inflammatory cellular infiltration and fibrin deposition among groups and for scanning transmission electron microscopic examinations to see the ultrastructural changes after CME. RESULTS: Survival analysis demonstrated that the cumulative survival rate of the 17 µm/500,000 group was significantly lower than that of the sham group (0/6 vs. 6/6, P = 0.001). The cumulative survival rate of the 17 µm/200,000 group was lower than those of the sham and 9 µm groups with no statistical difference (cumulative survival rate of the 17 µm/200,000, 9 µm/800,000, 9 µm/500,000, and sham groups was 4/6, 5/6, 6/6, and 6/6, respectively). The pathological alterations were similar between the 9 µm/500,000 and 9 µm/800,000 groups. The extent of inflammatory cellular infiltration and fibrin deposition was more severe in the 17 µm/200,000 group than in the 9 µm/500,000 and 9 µm/800,000 groups 3 and 10 days after the surgery. Scanning transmission electron microscopic examinations revealed platelet aggregation and adhesion, microthrombi formation, and changes in cardiomyocytes. CONCLUSION: The injection of 500,000 polystyrene microspheres at an average diameter of 9 µm is proved to be appropriate for the mouse model of CME based on the general conditions, postoperative survival rates, and pathological changes.
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Vasos Coronários/patologia , Vasos Coronários/cirurgia , Animais , Encéfalo/patologia , Oclusão Coronária/patologia , Oclusão Coronária/cirurgia , Vasos Coronários/ultraestrutura , Modelos Animais de Doenças , Embolização Terapêutica , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão e Varredura , Miocárdio/patologia , Agregação Plaquetária/fisiologiaRESUMO
The inflammatory response regulates congestive heart failure (CHF) development. T cell activation plays an important role in tissue inflammation. We postulate that CD28 or B7 deficiency inhibits T cell activation and attenuates CHF development by reducing systemic, cardiac, and pulmonary inflammation. We demonstrated that chronic pressure overload-induced end-stage CHF in mice is characterized by profound accumulation of activated effector T cells (CD3(+)CD44(high) cells) in the lungs and a mild but significant increase of these cells in the heart. In knockout mice lacking either CD28 or B7, there was a dramatic reduction in the accumulation of activated effector T cells in both hearts and lungs of mice under control conditions and after transverse aortic constriction. CD28 or B7 knockout significantly attenuated transverse aortic constriction-induced CHF development, as indicated by less increase of heart and lung weight and less reduction of left ventricle contractility. CD28 or B7 knockout also significantly reduced transverse aortic constriction-induced CD45(+) leukocyte, T cell, and macrophage infiltration in hearts and lungs, lowered proinflammatory cytokine expression (such as tumor necrosis factor-α and interleukin-1ß) in lungs. Furthermore, CD28/B7 blockade by CTLA4-Ig treatment (250 µg/mouse every 3 days) attenuated transverse aortic constriction-induced T cell activation, left ventricle hypertrophy, and left ventricle dysfunction. Our data indicate that CD28/B7 deficiency inhibits activated effector T cell accumulation, reduces myocardial and pulmonary inflammation, and attenuates the development of CHF. Our findings suggest that strategies targeting T cell activation may be useful in treating CHF.
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Abatacepte/farmacologia , Antígenos B7/metabolismo , Antígenos CD28/metabolismo , Insuficiência Cardíaca/fisiopatologia , Pneumonia/fisiopatologia , Análise de Variância , Animais , Antígenos B7/imunologia , Antígenos CD28/imunologia , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/imunologia , Distribuição Aleatória , Estatísticas não Paramétricas , Sístole/fisiologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Adequate hydration is recommended for acute ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) to prevent contrast-induced nephropathy (CIN). However, the optimal hydration regimen has not been well established in these high-risk patients. The objective of this study is to evaluate the efficacy of a preprocedural loading dose plus postprocedural aggressive hydration with normal saline guided by the left ventricular end-diastolic pressure (LVEDP) compared with general hydration for CIN prevention. The ATTEMPT study is a multicenter, open-label, investigator-driven, randomized controlled trial in China. Approximately 560 patients with STEMI undergoing primary PCI will be randomized (1:1) to receive either periprocedural general hydration (control group) or aggressive hydration (treatment group). Patients in the control group receive periprocedural general hydration with ≤500 mL normal saline (within 6 hours) at a normal rate (0.5 or 1 mL/kg · h). Patients in the treatment group receive a preprocedural loading dose (125/250 mL) of normal saline within 30 minutes and intravenous hydration at a normal rate until LVEDP is available, followed by postprocedural aggressive hydration guided by LVEDP for 4 hours and then continuous intravascular hydration at the normal rate until 24 hours after PCI. The primary end point is CIN, defined as a >25% or 0.5-mg/dL increase in serum creatinine from baseline during the first 48 to 72 hours after procedure. The ATTEMPT study has the potential to identify optimal hydration regimens for STEMI patients undergoing PCI.
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Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Hidratação/métodos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Cuidados Pré-Operatórios/métodos , Injúria Renal Aguda/induzido quimicamente , China/epidemiologia , Angiografia Coronária/métodos , Eletrocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro. METHODS: Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups. RESULTS: Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures. CONCLUSION: These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.
Assuntos
Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Peptídeos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Peçonhas/farmacologia , Animais , Células Cultivadas , Exenatida , Marcação In Situ das Extremidades Cortadas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/citologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RatosRESUMO
Transfemoral device occlusion and minimally invasive surgical repair are performed for doubly committed subarterial ventricular septal defect (dcVSD) to reduce the invasiveness of the conventional surgical repair through a median sternotomy. However, few studies have compared them in terms of effectiveness and cost. Inpatients with isolated dcVSD who had undergone transfemoral device occlusion or minimally invasive surgical repair from January 2011 to June 2014 were reviewed for a comparative investigation between the two procedures. Procedure success was achieved in 36 transfemoral (75 %) and in 36 surgical (100 %) procedures (p = 0.001). Transfemoral patients were older, with a VSD size similar to that of surgical patients (14.5 ± 11.7 vs 4.4 ± 2.9 years, p < 0.001; 4.5 ± 1.5 vs 4.4 ± 1.3 mm, p = 0.577, respectively). No significant difference was observed in complication rates between the two treatment groups (p = 1). No large residual shunt was observed. Small residual shunt was noted in two transfemoral patients and four surgical patients (p = 0.674). All these small residual shunts closed spontaneously during follow-up. The surgical repair costs 26 % less than the device occlusion (Yuan 22063.2 ± 343.9 vs Yuan 29970.1 ± 1335.2, p < 0.001), where most of the cost was attributed to the occluder in the amount of Yuan 19,500. Compared with device occlusion, minimally invasive surgical repair can provide superior efficacy and comparable complication rates. In addition, it is 26 % cheaper than device occlusion. In low-income countries where healthcare resources are limited, medical resources must be judiciously allocated to the treatment that allows for effective treatment of the largest number of patients.
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Comunicação Interventricular/economia , Comunicação Interventricular/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Dispositivo para Oclusão Septal/economia , Adolescente , Adulto , Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Aortic valve calcification (AVC) is a common progressive condition that involves several inflammatory and atherosclerotic mediators. However, it is unclear whether the occurrence of periprocedural myocardial injury (PMI) after elective coronary intervention is associated with AVC in stable coronary artery disease (CAD) patients. METHODS: A total of 530 stable CAD patients who underwent elective coronary intervention were enrolled in this clinical study. High sensitive cardiac troponin T (hs-cTnT) was detected before and after the procedure. PMI was defined as hs-cTnT after coronary intervention higher than 99th percentile upper reference limit (URL). All patients underwent echocardiography to detect the occurrence of AVC. Univariate and multivariate analyses were applied to analyze risk factors of PMI. RESULTS: A total of 210 patients (39.6 %) were diagnosed with PMI after elective coronary intervention. Compared with non-AVC patients (n = 386), AVC patients (n = 144) had higher rate of PMI (64.6 vs. 30.3 %, P < 0.01). CAD patients with AVC had higher Gensini score (39.9 ± 26.6 vs. 34.2 ± 22.1, P < 0.05) and more number of implanted stents (1.7 ± 0.8 vs. 1.5 ± 0.7, P < 0.05). After stratification by classic risk factors of CAD (such as age, male gender and diabetes) in subgroup analyses, we found that AVC patients had increased risk of PMI compared with non-AVC patients. Importantly, even after being adjusted by multivariate analysis, AVC still independently increased the risk of PMI (OR = 3.329, 95 % CI = 2.087-5.308, P < 0.01). CONCLUSION: AVC significantly increased the risk of PMI after elective coronary intervention. It could be one of the independent predictors for PMI in stable CAD patients.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Doença da Artéria Coronariana , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Calcinose/complicações , Calcinose/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Ecocardiografia/métodos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Lack of fluoroscopic landmarks can make valve deployment more difficult in patients with absent aortic valve (AV) calcification. The goal of this article was to evaluate the feasibility and effectiveness of transcatheter implantation of a valved stent into the AV position of a goat, assisted with a microcatheter which provides accurate positioning of coronary artery ostia to help valved stent deployment. METHODS: The subjects were 10 healthy goats in this study. A microcatheter was introduced into the distal site of right coronary artery (RCA) through femoral artery sheath. A minimal thoracic surgery approach was used to access the apex of the heart. The apex of the left ventricle was punctured; a delivery catheter equipped with the valved stent was introduced over a stiff guidewire into the aorta arch. We could accurately locate the RCA ostia through the microcatheter placed in the RCA under fluoroscopy. After correct valve position was confirmed, the valved stent was implanted after rapid inflation of the balloon. The immediate outcome of the function of the valved stents was evaluated after implantation. RESULTS: All ten devices were successfully implanted into the AV position of the goats. Immediate observation after the procedure showed that the valved stents were in the desired position after implantation by angiography, echocardiogram. No obstruction of coronary artery ostia occurred, and no moderate to severe aortic regurgitation was observed. CONCLUSIONS: When the procedure of transcatheter implantation of a balloon-expandable valved stent into the AV position of goats is assisted with microcatheter positioning coronary artery ostia, the success rate of operation can be increased in those with noncalcified AV.
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Substituição da Valva Aórtica Transcateter/métodos , Animais , Valva Aórtica/cirurgia , Feminino , Cabras , Implante de Prótese de Valva Cardíaca/métodos , MasculinoRESUMO
BACKGROUND: Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control. Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely, but 10%-20% of treated patients are nonresponders to radiofrequency denervation. The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN. METHODS: Seven swines randomly assigned to two groups: Renal cryoablation (CR) group and control group. The control group underwent renal angiogram only. The CR group underwent renal angiogram plus bilateral renal cryoablation. Renal angiograms via femoral were performed before denervation, after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis. Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves. RESULTS: Cryoablation did not induce severe complications at any time point. There was no significant change in diameter of renal artery. CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg. There was a slight but insignificant decrease in diastolic BP. The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation. Compared with the control group, renal tissue NE of CR group decreased by 89.85%. CONCLUSIONS: Percutaneous catheter-based cryoablation of the renal artery is safe. CR could effectively reduce NE storing in the renal cortex, and the efficiency could be maintained 28-day at least.