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1.
J Clin Med ; 10(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34362176

RESUMO

Hyperglycemia is associated with adverse outcomes after coronary artery bypass grafting (CABG). While there is a consensus that blood glucose control may benefit patients undergoing CABG, the role of biomarkers, optimal method, and duration of such monitoring are still unclear. The aim of this study is to define the efficacy of a continuous glucose monitoring system (CGMS) and link it to pro-inflammatory biomarkers while on insulin pump therapy in diabetic patients undergoing CABG. We prospectively assessed CGMS for 72 h in 105 patients including 52 diabetics undergoing isolated CABG. In diabetics, CGMS was connected to an insulin pump for precise glucose control. On top of conventional biomarkers (HbA1C, lipid profile), high sensitive C-reactive protein (hs-CRP), Regulated upon Activation Normal T cell Expressed and presumably Secreted (RANTES), and leptin levels were collected before surgery, 1 h, 12 h, 7 days, and at 1 year after CABG. Overall, CGMS revealed high glucose independently from underlying diabetes during first 48 h following CABG but was higher (p < 0.05) in diabetics. The insulin pump improved glycemic control over early follow-up (72 h) post-CABG. There were no hypoglycemic episodes in patients on insulin pump therapy and those receiving bolus insulin therapy. We revealed a lower rate of postpericardiotomy syndrome (PCTS) in patients on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (p = 0.03). Hs-CRP and RANTES levels were lower in patients with T2DM on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (p < 0.05). It is most likely due to the fact that insulin pump therapy decreases systemic inflammatory response. Further controlled trials should assess whether CGMS improves outcomes after cardiac surgery.

2.
Cardiology ; 139(2): 132-136, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29334682

RESUMO

BACKGROUND: High residual platelet reactivity (HRPR) during dual antiplatelet therapy (DAPT) may impact clinical outcomes following percutaneous coronary interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT loading may predict delayed maintenance HRPR is not clear. OBJECTIVE: The aim of this study was to determine whether conventional clinical or laboratory indices at loading before stenting may predict HRPR at 6 months of maintenance DAPT. METHODS: The study was designed on a single-center prospective cohort, and included 94 pre-PCI patients. All patients underwent elective PCI with drug-eluting stent implantation, and received DAPT with aspirin and clopidogrel. Platelet reactivity was assessed with 5 µmol/L of adenosine diphosphate-induced light transmission aggregometry before PCI, but after 24 h of DAPT loading, and repeated at 6 months. Baseline clinical characteristics, CYP2C19 polymorphism, C-reactive protein, soluble P-selectin, CD40L, interleukin-6, PAI-1 levels, and von Willebrand factor activity were analyzed. RESULTS: The incidence (light transmission aggregometry <50%) of prestent HRPR was 16%. By univariate regression, body mass index (BMI; p = 0.02), total cholesterol (p = 0.01), low-density lipoproteins (p = 0.004), CYP2C19*2 allele carriage (p = 0.006), soluble P-selectin (p = 0.009), and von Willebrand factor (p = 0.04) were linked to future HRPR. However, multivariate regression analysis suggested that only BMI and P-selectin were independent predictors of HRPR. CONCLUSIONS: Platelet reactivity before elective stenting is associated with numerous biomarkers; however, only BMI and soluble P-selectin were independent predictors of future HRPR during maintenance-phase DAPT. This may be important for future tailored antiplatelet strategies in patients with metabolic syndrome and diabetics.


Assuntos
Índice de Massa Corporal , Doença da Artéria Coronariana/sangue , Selectina-P/sangue , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Adulto , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos
4.
Sci Rep ; 6: 34913, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27734897

RESUMO

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.


Assuntos
Bilirrubina/química , Muramidase/química , Peptidil Dipeptidase A/química , Animais , Anticorpos Monoclonais/química , Células CHO , Estudos de Casos e Controles , Membrana Celular/metabolismo , Cricetinae , Cricetulus , Citometria de Fluxo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Mutação , Peptídeos/química , Fenótipo , Ligação Proteica , Domínios Proteicos , Proteína C Associada a Surfactante Pulmonar , Sarcoidose/sangue , Ressonância de Plasmônio de Superfície
5.
Cardiology ; 135(1): 36-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27188395

RESUMO

BACKGROUND: Prediction and potential prevention of sudden cardiac death (SCD) due to malignant ventricular arrhythmia (MVA) represent an obvious unmet medical need. We estimated the prognostic relevance of numerous biomarkers associated with future MVA development in patients with coronary artery disease (CAD) over 2 years of follow-up. METHODS: Patients with stable documented CAD (n = 97) with a mean age of 61 ± 10 years were prospectively enrolled in a single-center observational cohort study. Heart failure was diagnosed in 68% of the patients (NYHA class II-III). The mean left ventricular ejection fraction (LVEF) was 50 ± 13%, while 20% of patients had LVEF ≤35%. Sixty-two patients underwent myocardial revascularization during the follow-up (mean 25 ± 11 months). Clinical characteristics (age, gender, diabetes, history of coronary disease and arrhythmias, prior interventions and antecedent medications), noninvasive electrophysiological markers [microvolt T-wave alterations, signal-averaged electrocardiography, QT interval duration and alteration, and heart rate turbulence (HRT) and HR variability], laboratory indices [serum creatinine and creatinine clearance, brain natriuretic peptide (BNP), NT-proBNP, and C-reactive protein and troponin T levels] were assessed with regard to the MVA prognosis. RESULTS: MVA was diagnosed in 11 patients during the prospective follow-up. Prior percutaneous coronary intervention (p < 0.05), MVA or syncope (p < 0.05), on-pump coronary artery bypass grafting during follow-up (p < 0.01), LVEF ≤47% (p < 0.01), a left atrium size ≥4.7 cm (p < 0.05), left atrium index (p = 0.01), filtered QRS duration (p < 0.05), abnormal HRT (x03C7;2 = 6.2, p = 0.01) or turbulence slope (x03C7;2 = 9.5, p < 0.01), BNP ≥158 pg/ml (p < 0.01) and NT-proBNP ≥787 pg/ml (x03C7;2 = 4.4, p < 0.05) were significantly associated with MVA risk by univariate analysis. However, only prior MVA or syncope [odds ratio (OR) 11.1; 95% confidence interval (CI) 2.8-44.4; p < 0.01], abnormal HRT (x041E;R 13.6; 95% CI 2.8-66.1; p < 0.01) and plasma BNP (x041E;R 14.3; 95% CI 3.2-65.0; p < 0.01) remained independent predictors of MVA occurrence by multivariate Cox regression analysis. CONCLUSION: Prior syncope or MVA, HRT and elevated plasma BNP were independent MVA predictors, advocating for the prospective screening of high-risk CAD patients for potential SCD awareness.


Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/complicações , Morte Súbita Cardíaca , Taquicardia Ventricular/etiologia , Idoso , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Morte Súbita Cardíaca/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Prognóstico
6.
Cardiology ; 132(2): 74-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26111880

RESUMO

BACKGROUND: The landmark Dual Antiplatelet Therapy (DAPT) trial revealed an impressive reduction of stent thrombosis and myocardial infarction after prolonged 30-month DAPT compared to the conventional 12-month regimen. However, aside from the expected extra bleeding risks, more cancers and noncardiovascular deaths (NCVD) were observed in the 30-month DAPT arm. OBJECTIVE: We aimed to comprehend the totality of DAPT trial evidence in the light of the FDA medical review. RESULTS: A significant excess of solid cancers that was picked up after prasugrel treatment in the TRITON trial (Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes) and later observed with vorapaxar treatment in the TRACER trial (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) has now been confirmed by the FDA DAPT review for 30-month therapy with prasugrel [hazard ratio (HR) 1.3] and clopidogrel (HR 1.2). The latest randomized evidence with antiplatelet agents rejected the drug-specific cancer risks, clearly indicating the class effect. The NCVD risks were elevated after treatment with both thienopyridines, but were more prominent after clopidogrel treatment (HR 1.91) than prasugrel treatment (HR 1.17). About half of the NCVD were considered to be caused by cancers occurring after the 24 months of extended antiplatelet therapy. Impression: The DAPT trial confirmed that long-term antiplatelet therapy is associated with cancer that contributes to NCVD. Based on the full disclosure of cancer data by the DAPT study, it can be reflected that the optimal duration of antiplatelet therapy with thienopyridines should be limited to no more than 2 years. This duration allows the preservation of most vascular benefits while avoiding additional cancers and NCVD. © 2015 S. Karger AG, Basel.

7.
Cardiology ; 129(2): 103-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25227134

RESUMO

OBJECTIVE: To detect residual platelet aggregation following the switch from generic (GC) to brand clopidogrel (BC) in male patients after ST-elevated myocardial infarction (STEMI). METHODS: The study was designed as an open-label, prospective cohort trial. Thirty-three male STEMI patients were enrolled. All patients received dual antiplatelet therapy with aspirin (100 mg/daily) and one of six GC at a daily dose of 75 mg. After 2 weeks, all patients were switched to BC. Adrenaline- and adenosine diphosphate (ADP)-induced platelet aggregation was assessed twice: on day 14 (before the switch) and on day 21 (after 1 week of BC therapy). RESULTS: Adrenaline-induced platelet aggregation did not differ among clopidogrel formulations. In contrast, residual 5 µM ADP-induced platelet aggregation after BC differs from GC by 14% (28.0 ± 2.5 vs. 23.9 ± 2.1%; p = 0.03). When 20 µM ADP was used as agonist, the difference was smaller (36.2 ± 2.9 vs. 34.6 ± 2.8%) but still significant (p = 0.04) favoring BC. CONCLUSIONS: After 2 weeks of therapy, switching from GC to BC was associated with a mild but significant reduction in ADP-induced platelet aggregation in male post-STEMI patients. The observed differences between GC and BC should be confirmed in a larger randomized study, but may represent a risk in underdeveloped countries, where GC therapy is mandatory for post-MI inpatients.


Assuntos
Substituição de Medicamentos , Medicamentos Genéricos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Difosfato de Adenosina/farmacologia , Aspirina/uso terapêutico , Clopidogrel , Quimioterapia Combinada , Epinefrina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Estudos Prospectivos , Ticlopidina/uso terapêutico
8.
Stroke Res Treat ; 2014: 302824, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24955279

RESUMO

Postoperative cognitive dysfunction (POCD) is a mild form of perioperative ischemic brain injury, which emerges as memory decline, decreased attention, and decreased concentration during several months, or even years, after surgery. Here we present results of our three neuropsychological studies, which overall included 145 patients after on-pump operations. We found that the auditory memory span test (digit span) was more effective as a tool for registration of POCD, in comparison with the word-list learning and story-learning tests. Nonverbal memory or visuoconstruction tests were sensitive to POCD in patients after intraoperative opening of cardiac chambers with increased cerebral air embolism. Psychomotor speed tests (digit symbol, or TMT A) registered POCD, which was characteristic for elderly atherosclerotic patients. Finally, we observed that there were significant effects of the order of position of a test on the performance on this test. For example, the postoperative performance on the core tests (digit span and digit symbol) showed minimal impairment when either of these tests was administered at the beginning of testing. Overall, our data shows that the selection of tests, and the order of which these tests are administered, may considerably influence the results of studies of POCD.

9.
Stroke Res Treat ; 2011: 980873, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21776370

RESUMO

Cardiac surgery is commonly associated with brain ischemia. Few studies addressed brain electric activity changes after on-pump operations. Eyes closed EEG was performed in 22 patients (mean age: 45.2 ± 11.2) before and two weeks after valve replacement. Spouses of patients were invited to participate as controls. Generalized increase of beta power most prominent in beta-1 band was an unambiguous pathological sign of postoperative cortex dysfunction, probably, manifesting due to gamma-activity slowing ("beta buzz" symptom). Generalized postoperative increase of delta-1 mean frequency along with increase of slow-wave activity in right posterior region may be hypothesized to be a consequence of intraoperative ischemia as well. At the same time, significant changes of alpha activity were observed in both patient and control groups, and, therefore, may be considered as physiological. Unexpectedly, controls showed prominent increase of electric activity in left temporal region whereas patients were deficient in left hemisphere activity in comparison with controls at postoperative followup. Further research is needed in order to determine the true neurological meaning of the EEG findings after on-pump operations.

10.
Cardiol Res Pract ; 2010: 143679, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20631826

RESUMO

Background. Microemboli are a widely recognized etiological factor of cerebral complications in cardiac surgery patients. The present study was aimed to determine if size of left cardiac chambers relates to cerebral microembolic load in open heart operations. Methods. Thirty patients participated in the study. Echocardiography was performed in 2-3 days before surgery. A transcranial Doppler system was used for registering intraoperative microemboli. Results. Preoperative left atrium and left ventricular end-systolic and end-diastolic sizes significantly correlated with intraoperative microembolic load (rs = 0.48, 0.57 and 0.53, Ps < .01, resp.). The associations between left ventricular diameters and number of cerebral microemboli remained significant when cardiopulmonary bypass time was included as a covariate into the analysis. Conclusions. The present results demonstrate that increased size of left heart chambers is an influential risk factor for elevated cerebral microembolic load during open heart operations. Mini-invasive surgery and carbon dioxide insufflation into wound cavity may be considered as neuroprotective approaches in patients with high risk of cerebral microembolism.

12.
Int J Cardiol ; 126(3): 448-9, 2008 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-17477988

RESUMO

Effects of psychological traits on heart rate (HR) and heart rate variability (HRV) were evaluated in patients awaiting cardiac surgery. Alexithymics demonstrated slowed HR, whereas high cognitive performance was associated with elevated HR in 2-3 days before surgery. Depression negatively correlated with HRV low frequency power. These data are consistent with previous findings of diverse moderate stress effects on HR regulation in cardiologic patients and healthy subjects in accordance to differences in psychological characteristics.


Assuntos
Sintomas Afetivos/diagnóstico , Arritmias Cardíacas/epidemiologia , Procedimentos Cirúrgicos Cardíacos/mortalidade , Transtorno Depressivo/diagnóstico , Complicações Pós-Operatórias/mortalidade , Adulto , Sintomas Afetivos/complicações , Idoso , Ansiedade/complicações , Ansiedade/diagnóstico , Arritmias Cardíacas/psicologia , Procedimentos Cirúrgicos Cardíacos/métodos , Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico , Estudos de Coortes , Doença das Coronárias/psicologia , Doença das Coronárias/cirurgia , Transtorno Depressivo/complicações , Feminino , Frequência Cardíaca/fisiologia , Doenças das Valvas Cardíacas/psicologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/psicologia , Cuidados Pré-Operatórios , Probabilidade , Valores de Referência , Estresse Psicológico , Análise de Sobrevida
13.
Cerebrovasc Dis ; 23(1): 50-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16968987

RESUMO

BACKGROUND: The aim of the study was to determine the effects of asymmetric cerebral embolic load on cognitive functions. METHODS: Thirty-six open heart surgery (OH) and 26 coronary artery bypass grafting (CABG) patients were evaluated by neuropsychological and transcranial Doppler tests. RESULTS: OH was associated with a significantly larger microembolic load in comparison to CABG. In OH patients, the microembolic load at the left middle cerebral artery correlated with a verbal memory decline, whereas the microembolic load at the right middle cerebral artery correlated with a nonverbal memory deficit. CABG patients also showed a postoperative verbal memory decline which correlated with cardiopulmonary bypass length but not with microembolic load. CONCLUSION: Massive microembolic load during OH induces specific cognitive impairment in accordance to the brain region to which they are delivered. In atherosclerotic patients, the left temporal region is especially prone to perioperative ischemia.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Transtornos Cognitivos/etiologia , Embolia Intracraniana/etiologia , Adolescente , Adulto , Idoso , Doenças da Aorta/complicações , Aterosclerose/complicações , Transtornos Cognitivos/fisiopatologia , Estudos de Coortes , Ponte de Artéria Coronária/efeitos adversos , Feminino , Lateralidade Funcional , Cardiopatias/complicações , Cardiopatias/cirurgia , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/etiologia , Embolia Intracraniana/diagnóstico por imagem , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Fatores de Tempo , Ultrassonografia Doppler Transcraniana , Ultrassonografia de Intervenção
14.
Brain Res Brain Res Rev ; 50(2): 266-74, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16198423

RESUMO

Patients who underwent cardiac surgery and their relatives often complain on postoperative memory impairment. Most prospective neuropsychological studies also found postoperative cognitive decline early after surgery. Nevertheless, recently several reports questioned the existence of long-term brain alterations in these patient cohorts. The present review was aimed to clear up the true cardiac surgery effects on brain and cognitive functions. The reviewed data evidence that cardiac surgery interventions induce persistent localized brain ischemic lesions along with rapidly reversing global brain swelling and decreased metabolism. A range of studies showed that left temporal region was especially prone to perioperative ischemic injury, and these findings might explain persistent verbal short-term memory decline in a considerable proportion of cardiac surgery patient cohorts. Speed/time of cognitive performance is commonly decreased early after on-pump surgery either. Nevertheless, no association between psychomotor speed slowing and intraoperative embolic load was found. The rapid recovery of the latter cognitive domain might be better explained by surgery related acute global brain metabolism changes rather than ischemic injury effects. Hence, analyses of performance on separate cognitive tests rather than summarized cognitive indexes are strongly recommended for future neuropsychological studies of cardiac surgery outcomes.


Assuntos
Isquemia Encefálica/complicações , Transtornos Cognitivos/etiologia , Cardiopatias/cirurgia , Período Pós-Operatório , Cirurgia Torácica , Animais , Humanos , Testes Neuropsicológicos , Fatores de Tempo
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