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Επαγωγή μετισχαιμικής προστασίας με εξωγενή χορήγηση H2S σε αναισθητοποιημένους κονίκλους. Μελέτη του μηχανισμού δράσηςΜπιμπλή, Σοφία-Ίρις 29 April 2014 (has links)
Η μοριακή σηματοδότηση κατά την αρχή της επαναιμάτωσης η οποία οδηγεί σε προστασία του μυοκαρδίου περιλαμβάνει το μονοπάτι διάσωσης NO/cGMP/PKG/KATP, το μονοπάτι διάσωσης των κινασών RISK(PI3K/Akt, ERK 1/2, GSK3β) και το μονοπάτι JAK/STAT έχοντας ως τελικό στόχο την αναστολή της διάνοιξης των mPTP, το οποίο θεωρείται το τελικό σημείο της επαγόμενης καρδιοπροστασίας. Η παραγωγή του H2S εμπλέκεται στους μηχανισμούς της ισχαιμικής προετοιμασίας και της μετισχαιμικής προστασίας. Διάφορες μελέτες σε απομονωμένα μυοκάρδια (Langendorff isolated perfused hearts) υποστηρίζουν ότι η επαγωγή της καρδιοπροστασίας από την εξωγενή χορήγηση H2S επιτυγχάνεται μέσω της ενεργοποίησης των KATP διαύλων. Ωστόσο, δεν υπάρχουν ολοκληρωμένες μελέτες οι οποίες να καταδεικνύουν τους μοριακούς μηχανισμούς οι οποίοι εμπλέκονται στην καρδιοπροστατευτική δράση του συγκεκριμένου αέριου διαβιβαστή σε in vivo πειραματικά μοντέλα.
Ο σκοπός της παρούσας μελέτης είναι ο έλεγχος της υπόθεσης ότι η θεραπευτική χορήγηση ενός ανόργανου δότη H2S (NaHS) στο τέλος της ισχαιμίας και κατά την επαναιμάτωση μειώνει την έκταση του εμφράγματος του μυοκαρδίου σε αναισθητοποιημένους κόνικλους. Επιπλέον μελετήθηκαν οι υποκείμενοι μοριακοί μηχανισμοί.
Αναισθητοποιημένοι αρσενικοί κόνικλοι Νέας Ζηλανδίας διαχωρίσθηκαν σε 7 ομάδες και υπεβλήθησαν σε 30 λεπτά παρατεταμένης/συνεχούς ισχαιμίας του μυοκαρδίου ακολουθούμενης από 3 ώρες επαναιμάτωσης με τις ακόλουθες παρεμβάσεις: 1) Ομάδα ελέγχου (control) : χωρίς περαιτέρω παρεμβάσεις, 2) Ομάδα NaHS: χορήγηση ενός δότη Η2S (ΝaΗS) με IV bolus έγχυση και δόση 100μg/kg στο 20 λεπτό της ισχαιμίας ακολουθούμενη από έγχυση σταθερού ρυθμού με δόση 1mg . kg-1 . h-1 για τα επόμενα 120 λεπτά , 3) Ομάδα ΝaHS και DT-2: χορήγηση ΝaHS όμοια με την ομάδα 2 και DT-2 με IV bolus έγχυση και δόση 0,25 mg. kg-1 10 λεπτά πριν την παρατεταμένη ισχαιμία, 4) Ομάδα TAT και ΝaHS: χορήγηση NaHS όμοια με την ομάδα 2 και ΤΑΤ με IV bolus έγχυση και δόση 0.143 mg. kg-1 10 λεπτά πριν την παρατεταμένη ισχαιμία (Η δόση επελέγει ισομοριακά ως προς το DT-2), 5) Ομάδα NaHS+5-HD: χορήγηση NaHS όμοια με την ομάδα 2 και 5-HD με IV bolus έγχυση σε δόση 5mg/kg 40 λεπτά πριν την παρατεταμένη ισχαιμία., 6) Ομάδα NaHS+L Name: χορήγηση NaHS όμοια με την ομάδα 2 και L Name με IV bolus έγχυση σε δόση 10mg/kg στο 19 λεπτό της παρατεταμένης ισχαιμίας, 7) Ομάδα NaHS+Wortmannin: χορήγηση NaHS όμοια με την ομάδα 2 και Wortmannin με IV bolus έγχυση σε δόση 60μg/kg στο 19 λεπτό της παρατεταμένης ισχαιμίας.
Μετά το τέλος των πειραμάτων εκτιμήθηκε η εμφραγματική(Ι) και η περιοχή σε κίνδυνο (R). Σε δεύτερη σειρά πειραμάτων ελέγθηκε η ενεργοποίηση των Akt, ERK 1/2 ,eNOS, GSK3β, STAT3, VASP και της PLB σε δείγμα ισχαιμικού ιστού των ομάδων ελέγχου, NaHS και NaHS + DT-2. Για επιβεβαίωση της μη φωσφορυλίωσης ορισμένων από τις προαναφερθείσες πρωτεΐνες χρησιμοποιήθηκε ως ομάδα αναφοράς, μία πρόσθετη ομάδα PostC η οποία υπεβλήθη σε 30 λεπτά παρατεταμένη ισχαιμίας ακολουθούμενης από 10 λεπτά επαναιμάτωσης στην έναρξη της οποίας εφαρμόσθηκαν 8 κύκλοι των 30 δευτερολέπτων ισχαιμίας/επαναιμάτωσης.
Ο δότης H2S, NaHS, μείωσε την έκταση του εμφράγματος σε σύγκριση με την ομάδα ελέγχου(12.3±3.3% vs 46.4±1.8%,p<0.05), ενώ η προσθήκη του DT-2 ανέστειλε την καρδιοπροστατευτική δράση του NaHS(39.8±3.4%,p=NS vs Control). Η χορήγηση του πεπτιδίου ελέγχου ΤΑΤ δεν τροποποίησε τη δράση του NaHS(23.0±3.4%,p=NS vs H2S group). Ο αναστολέας διάνοιξης των mitoKATP (5-HD) και της ενεργότητας της eNOS (L-NAME) δεν μείωσε την ανασταλτική δράση του NaHS στην έκταση του εμφράγματος(14.1±2.0% και 14.7±2.2% αντίστοιχα, p=NS). Ωστόσο, η χορήγηση του αναστολέα των PI3K/Akt (wortmannin) ανέστρεψε την καρδιοπροστατευτική δράση του NaHS(41.8±1.4% vs 12.3±3.3%, p<0.05). Η φωσφορυλίωση των VASP,και PLB ήταν σημαντικά υψηλότερη στην ομάδα NaHS σε σχέση με τις ομάδες ελέγχου και NaHS+DT-2,οι ERΚ 1/2 φωσφορυλιώθηκαν στις ομάδες NaHS και PostC σε σχέση με τις ομάδες ελέγχου και NaHS+DT-2, οι Akt και STAT3 ήταν εξίσου ενεργοποιημένες στις ομάδες NaHS, NaHS+DT-2 και PostC σε σχέση με την ομάδα ελέγχου, ενώ δεν παρατηρήθηκε φωσφορυλίωση των eNOS και GSK3β στις ομάδες ελέγχου, ΝaHS και NaHS+DT-2 σε σχέση με την ομάδα PostC.
Η εξωγενής χορήγηση H2S στο τέλος της παρατεταμένης ισχαιμίας και κατά την επαναιμάτωση επάγει φαρμακολογική μετισχαιμική προστασία σε αναισθητοποιημένους κόνικλους μέσω των μονοπατιών Akt/PKG/PLB και PKG/ ERK 1/2 ανεξάρτητα από την eNOS, την GSK3β, το JAK/STAT μονοπάτι και την διάνοιξη των mitoKATP. / The signal transduction pathways which are recruited during early reperfusion include the nitric oxide/cGMP/PKG/KATP pathway, the reperfusion injury salvage kinase pathway (PI3K /Akt, ERK 1/2, GSK3α), and the JAK/STAT pathway targeting the inhibition of mPTP opening which is considered the end-point for inducing cardioprotection. The production of H2S plays a role in myocardial pre-and post-conditioning responses. Several studies in isolated hearts support cardioprotection from exogenous H2S due to KATP channels activation. However, there is a lack of evidence for the molecular mechanism underlying the protection of H2S in in vivo experimental models of ischemia/reperfusion injury.
The aim was to elucidate the hypothesis that therapeutic administration of the H2S donor NaHS before and during reperfusion reduces the infarct size in anesthetized rabbits. Additional the molecular mechanisms underlying the induced cardioprotection from exogenous administrated H2S were studied.
Anesthetized male rabbits were divided into 7 groups and were subjected to 30 min regional ischemia of the heart and 3 hours reperfusion with the following additional interventions: 1) Control group no further intervention, 2) NaHS group was treated with the H2S donor sodium hydrosulphide (NaHS) at a dose of 100 ιg.Kg-1 bolus on the 20th min of ischemia followed by infusion of 1mg.Kg-1. h-1 for the next 120 min, 3) NaHS +DT-2 group, treated with NaHS and the PKG inhibitor DT-2 that was given at a dose of 0.25 mg.kg-1 bolus 10 min before sustained ischemia, 4) NaHS +TAT group, treated with NaHS and the control peptide TAT that was given at a dose of 0.143 mg.kg-1 bolus 10 min before sustained ischemia, 5) NaHS+5-hydroxydecanoic acid (5-HD) treated with NaHS and mitoKATP channels inhibitors 5-HD iv bolus 40 minutes before occlusion at a dose of 5 mg.kg-1, 6) NaHS+ L-NAME treated with NaHS and the synthase of NO inhibitor L NAME IV bolus on the 19th min of ischemia at a dose of 10 mg.kg-1 and 7) NaHS+ Wortmannin treated with NaHS and the PI3/Akt inhibitor Wortmannin on the 19th min of ischemia at a dose of 60ιg.kg-1. After the end of the experiments the infarct size (I) and the area at risk (R) were estimated. In a second series of experiments, determination of activation of Akt, ERK 1/2 ,eNOS, GSK3α, STAT3, VASP and phopsholamban (PLB) was investigated in tissue samples from ischemic area of myocardium from Control, NaHS and NaHS
+ DT-2 groups. As positive control of no phosphorylation observed, PostC group was used. In PostC group animals were subjected in 30 minutes sustained ischemia followed by 10 minutes of reperfusion, were 8 cycles of 30 seconds of ischemia/ reperfusion were applied immediately after the onset of reperfusion. H2S donor NaHS reduced the infarct size compared to Control (12.3 ± 3.3% vs 46.4 ± 1.8%, p<0.05), whereas the addition of the PKG inhibitor DT2 abrogated the infarct size limiting effect (39.8 ± 3.4%, p=NS vs Control). Treatment with the control peptide TAT did not alter the effect of NaHS (23.0 ± 3.4%, p=NS vs H2S group). Administration of mitoKATP inhibitor (5-HD) and eNOS inhibitor (L-NAME) did not alter the infract limiting effects of NaHS (14.1±2.0% and 14.7±2.2% respectively, p=NS). However, administration of the PI3K/Akt inhibitor wortmannin reversed this cardioprotection (41.8±1.4% vs 12.3±3.3%, p<0.05). Phosphorylation of VASP, ERK ½ and PLB was significantly higher in NaHS treated group versus control and NaHS+DT-2 groups, in PostC group ERK ½ were phosphorylated respectively to NaHS treated group, Akt and STAT3 were phosphorylated in NaHS, NaHS+DT-2 and PostC groups vs Control group, whereas no phosphorylation of eNOS and GSK3α was observed in NaHS, NaHS+DT-2 and control groups compared to PostC group.
Exogenous administration of H2S at the end of ischemia and during reperfusion induces pharmacological postconditioning in anesthetized rabbits due to Akt/PKG/PLB and PKG/ ERK 1/2 activation independently of eNOS, GSK3α, JAK/STAT and mitoKATP activation.
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Acute Pharmacological Treatment given to Older Adults with Acute Myocardial Infarction: A Nationwide Emergency Department Study, 1992-2010Alowayesh, Maryam S 23 April 2013 (has links)
OBJECTIVES: To determine the pattern and predictors of use of antiplatelet agents and beta-blockers given in the emergency department (ED) to older adults with acute myocardial infarction (AMI) and its effects on in-hospital mortality and length of hospital stay (LOS) and to determine the effect of computerized ED guideline reminders on their utilization. METHODS: A cross-sectional study using the National Hospital Ambulatory Medical Care Survey (NHAMCS) ED data for years 1992 to 2010 was conducted. Patients were included if they had an admission diagnosis of AMI (ICD-9-CM code 410.xx) and were ≥55 years. Survey logistic regression was used to examine whether there was a trend in the use of antiplatelet agents and beta-blockers across the years and to explore the association between various predictor variables, including ED computerized guideline reminders, and their utilization rates. The chi-square test was used to see whether users of these drugs were different from non-users in their rates of in-hospital mortality. Survey linear regression was used to explore the effect of utilization of these drugs on LOS. All the visits were weighted to get national estimates. All of the analyses were carried out with SAS 9.3 statistical package. RESULTS: A total of 1,771 visits (weighted frequency = 6.1 million) were eligible for this study. Both antiplatelet agents and beta-blockers were shown to have a positive trend across the years. Age, sex, chest pain, triage, using an ambulance, and metropolitan region were all found to be significant predictors of either antiplatelet agent or beta-blocker utilization. Use of beta-blockers was associated with lower in-hospital mortality. Neither drug class had an effect on LOS. Finally, patients who were treated in EDs with computerized guideline reminders were twice as likely to get an antiplatelet agent, but this was not seen with beta-blockers. CONCLUSION: This study displayed a positive pattern across the years in the use of antiplatelet agents and beta-blockers given to older AMI patients. It also showed that age, sex, and other important variables were significant predictors of their utilization. The use of beta-blockers yielded lower in-hospital mortality. Finally, the use of ED reminders increased antiplatelet agent utilization.
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Associação entre tempestades geomagnéticas e internações por infarto agudo do miocárdio / Association between geomagnetic activity and daily hospitalization by acute myocardial infarction.Kutschenko, Andressa 19 December 2012 (has links)
Os diversos fenômenos solares mostram que a sua atividade não é constante, sendo as manchas solares observadas em sua fotosfera um indicador de atividade do Sol. Os números dessas manchas seguem um ciclo de 11 anos que alterna entre máximos e mínimos; quanto maior o número de manchas, maior o número de erupções no Sol. A literatura médica vem mostrando algumas evidências de que a atividade solar possui alguma relação com a predisposição das pessoas a algumas doenças. As tempestades geomagnéticas são associadas a doenças cardiovasculares, mudanças na pressão arterial sistólica, gravidade da crise de enxaqueca, distúrbios psiquiátricos. As condições da atividade geomagnética são classificadas segundo Batista (2003) em uma escala de Calma, Transição, Ativo, Tempestade fraca, Tempestade intensa ou Tempestade muito intensa. No presente projeto de pesquisa, objetiva-se investigar a associação entre atividade geomagnética e internações diárias por infarto nos hospitais de Ribeirão Preto e região, no período de 1998 a 2007. A hipótese em estudo é que em dias de condições de atividade geomagnética muito perturbada, o número médio de internações por doenças isquêmicas do coração é maior. Para a análise dos dados foi utilizado o modelo de regressão de Poisson com função logarítmica com o auxílio do software SAS 9.2, utilizando o procedimento PROC GENMOD. Observa-se que há evidências de associação entre tempestades geomagnéticas e internações por IAM. / Numerous solar phenomena demonstrate that their activities are not continual, and sunspots noticed in their photosphere are considered an indicator by Suns activity. Numbers linked with these sunspots follow an eleven-year cycle, which alternates between high and low, it means, the greater the number of sunspots, the greater the number of Sun eruptions. Medical Literature has produced evidences that solar activity has some association with people predisposing to some diseases. Geomagnetic storms are related with cardiovascular disease, changes in systolic blood pressure, severity and psychiatric disorders. According to Batista (2003), geomagnetic activity conditions are categorized on a scale of Quiet, Transition, Acting, Weak Storm, Intense Storm or Very Intense Storm. This study intends to investigate the association between geomagnetic activity and daily hospitalization by acute myocardial infarction (AMI) in Ribeirão Preto and its region from 1998 to 2007. The hypothesis being studied is that: day which has unquiet geomagnetic condition, the average number of hospitalizations originated by ischemic heart disease is higher. In order to get on with data analysis, it was used Poissons regression model, with logarithmic function through SAS 9.2, using PROC GENMOD procedure. In consequence, it is observed that there are evidences between geomagnetic storms and hospitalizations by AMI.
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Avaliação das variáveis de desempenho no tratamento das síndromes isquêmicas miocárdicas instáveis no Brasil: análise do registro BRACE (Brazilian Registry in Acute Coronary Syndromes) / Performance Measures for the treatment of acute coronary syndromes in Brazil: analysis of the Brazilian Registry in Acute Coronary syndromEs (BRACE)Franken, Marcelo 17 May 2016 (has links)
INTRODUÇÃO: A utilização de medidas diagnósticas e terapêuticas tem impacto significativo na morbidade e mortalidade associadas a síndromes miocárdicas isquêmicas instáveis (SIMI). A quantificação do uso destas medidas permite mensurar a qualidade no atendimento ao paciente por diferentes instituições de saúde, países ou regiões. Dados a respeito da utilização de medidas de desempenho no atendimento a pacientes com SIMI são escassos no Brasil, e a coleta de dados confiáveis a esse respeito é o objetivo do Registro Brasileiro de Síndromes Coronárias Agudas (BRACE). MÉTODOS: BRACE é um registo epidemiológico transversal, observacional de pacientes com SIMI. Para seleção dos hospitais foi adotada a metodologia de \"amostragem por conglomerados\", estratificada por região, característica de ensino (universitário ou não) e entidade mantenedora (público ou privado) para se obter uma imagem representativa de pacientes com SIMI no país. Escore de desempenho que varia de 0 a 100% foi desenvolvido para comparar os parâmetros estudados. As variáveis de desempenho isoladamente e as pontuações do escore foram comparados entre os tipos de instituições e a relação entre a pontuação de desempenho e os desfechos foram avaliados. RESULTADOS: 1.150 pacientes com idade média de 63 anos, 64% do sexo masculino, de 72 hospitais foram incluídos no registro. O escore desempenho médio para a população geral foi de 65,9% ± 20,1%. Instituições de ensino tiveram uma pontuação de desempenho significativamente mais elevada (71,4% ± 16,9%) em comparação com os hospitais não docentes (63,4% ± 21%; p < 0,001). A mortalidade hospitalar foi de 5,2%, e as variáveis que se correlacionaram significativamente e de forma independente com a mortalidade intra-hospitalar foram: idade - por ano (OR = 1,06, 95% IC 1,04-1,09, P < 0,001), doença renal crônica (OR = 3,59 , 95% IC 1,32-9,75, P= 0,012), angioplastia prévia (OR = 0,23, 95% IC 0,07-0,77, P= 0,017) e escore de desempenho - por ponto de aumento (OR = 0,97, 95% IC 0,96-0,98, P < 0,001). CONCLUSÃO: Os dados deste estudo demonstram que o uso de ferramentas de diagnóstico e abordagens terapêuticas para o tratamento das SIMI é distribuído de forma heterogênea e inferior ao ideal no Brasil, e que o escore de desempenho está associado de forma independente a mortalidade intrahospitalar / BACKGROUND: The use of diagnostic and therapeutic tools has a significant impact on morbidity and mortality associated with acute coronary syndromes (ACS). Data about the utilization of ACS performance measures are scarce in Brazil, and improving its reliable collection is an objective of the Brazilian Registry in Acute Coronary syndromEs (BRACE). METHODS: BRACE is a cross-sectional, observational epidemiological registry of ACS patients. Stratified \"cluster sampling\" methodology was adopted to obtain a representative picture of ACS in the country. A performance score varying from 0 to 100 was developed to compare the studied parameters. The performance measures alone and the performance scores were compared between institutions, and the relationship between the performance score and outcomes was evaluated. RESULTS: 1,150 patients median age 63 years, 64% male, from 72 hospitals were included in the registry. The mean performance score for the overall population was 65.9%±20.1%. Teaching institutions had a significantly higher performance score (71.4% ± 16.9%) compared to non-teaching hospitals (63.4% ± 21%; P < 0.001). In-hospital mortality was 5.2%, and the variables that correlated significantly and independently with in-hospital mortality included age - per year (OR=1.06, 95% CI 1.04-1.09, P < 0.001), chronic kidney disease (OR=3.59, 95% CI 1.32-9.75, P=0.012), prior angioplasty (OR=0.23, 95% CI 0.07-0.77, P=0.017) and performance score - per point increase (OR=0.97, 95% CI 0.96-0.98, P < 0.001). CONCLUSION: Data from this study demonstrate that use of diagnostic tools and therapeutic approaches for the management of ACS is heterogeneous and less than ideal in Brazil, and that performance score is independently associated with in-hospital mortality
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Expression and function of the formyl peptide receptor 2 in experimental myocardial infarctBena, Stefania January 2014 (has links)
In Acute Myocardial Infarction (AMI), inflammation is a prerequisite for healing but it can paradoxically extend tissue injury; hence it needs to be modulated. Here, we investigated the role of the pro resolving GPCR FPR2/ALX and its agonist Annexin A1 (AnxA1) in AMI using mice lacking of the Fpr2/3 genes and with an in-frame GFP gene ‘knocked-in’. We developed protocols aimed to determine GFP expression as an indication of Fpr2 gene activity. Also, the Left Anterior Descending Coronary Artery of male Fpr2/3 KO and littermate controls (WT) was occluded for 30min and re-opened for 90min. At the end tissue injury and inflammatory response were studied. A significant proportion of Fpr2/3 KO perished during the procedure. The rest survived up to 90 min and exhibited a larger infarct size, with higher troponin I and inflammation markers (KC, TNFα) than WT animals. At the end of reperfusion, Fpr2/3 KO displayed an unbalanced production of pro and anti-inflammatory lipids (higher PGE2, PGI2, LTB4 and attenuated PGA1, RvD2, LXA4) and a deregulated activation of the cardioprotective IL-6/JAK/STAT3 signalling. Administration of AnxA1 afforded cardioprotection (reduction of infarct size; Troponin I, Caspase3 activity and TNFα) in WT but not in Fpr2/3 KO. A parallel in vitro investigation on the functional FPR2/ALX domains required by AnxA1 and other agonists was also conducted. HEK-293 cells transfected with FPR1, FPR2/ALX and FPR1/FPR2 chimeric receptor were used and calcium flux, 4 pERK and gene modulation analysed. AnxA1 required the N-terminus and the II and III extracellular loops of FPR2/ALX to evoke canonical responses. SAA interacted/activated the I and the II extracellular loops of FPR2/ALX, whereas the compound 43 suffices the I extracellular loop. In summary, the FPR2/AnxA1 pathway exerts a protective role in AMI. AnxA1 mimetic that activated selective FPR2/ALX domains can be synthetize to prevent tissue damage caused by AMI.
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Avaliação dos efeitos da co-administração dos hormônios da tireoide e do carvedilol sobre o coração de ratos Wistar submetidos ao infarto agudo do miocárdioOrtiz, Vanessa Duarte January 2018 (has links)
Introdução: Após o infarto agudo do miocárdio (IAM), o tratamento com hormônios da tireoide (HT) vem revelando efeitos cardioprotetores. Os HT, todavia, provocam uma estimulação adrenérgica, induzindo elevação da frequência cardíaca, a qual contribui para progressão da disfunção ventricular após o IAM. O betabloqueador carvedilol, entretanto, é capaz de bloquear a estimulação adrenérgica. Objetivo: Avaliar o efeito da administração conjunta dos HT e do carvedilol sobre o coração de ratos submetidos ao IAM. Nesse contexto, enfocar nos efeitos dessa coadministração sobre o remodelamento ventricular, a função cardíaca e o estresse oxidativo. Materiais e métodos: Ratos Wistar machos foram divididos em cinco grupos (n=8-10/grupo): grupo sham (SHAM), grupo infarto (IM), grupo infarto+HT (IM+HT), grupo infarto+carvedilol (IM+C) e grupo infarto+C+HT (IM+C+HT). Após o IAM, os grupos SHAM e IM receberam salina, e os tratados receberam seus respectivos tratamentos por 12 dias por gavage. Após esse período, os animais foram submetidos a uma avaliação ecocardiográfica, e, posteriormente, ao cateterismo venticular. Em seguida, os animais foram eutanasiados para a coleta do coração, do pulmão e do fígado, para análises morfométricas e bioquímicas. Análise estatística: ANOVA de uma via seguida pelo teste de Student-Newman-Keuls. Nível de significância P<0,05. Resultados: A respeito dos parâmetros morfométricos, foi possível verificar hipertrofia cardíaca nos grupos infartados tratados em relação aos grupos SHAM e IM. Quanto aos parâmetros ecocardiográficos, os grupos tratados demonstraram aumento da espessura da parede posterior na sístole, da fração de ejeção e redução do índice de tensão de parede em comparação ao grupo IM. Os grupos IM+C e IM+C+HT também apresentaram atenuação da redução da mudança de área fracional e do aumento do volume sistólico final em relação aos grupos IM e IM+HT. Quanto aos parâmetros hemodinâmicos, houve redução das dP/dt máxima e mínima, da pressão sistólica do ventrículo esquerdo (VE) e aumento da pressão diastólica final do VE no grupo IM em comparação ao SHAM. Entretanto, todos esses parâmetros foram revertidos nos grupos tratados. A frequência cardíaca aumentou nos grupos IM+HT e IM+C+HT em relação aos outros grupos, mas reduziu no grupo IM+C+HT em relação ao grupo IM+HT. Quanto aos parâmetros de estresse oxidativo, verificou-se aumento dos níveis de espécies reativas de oxigênio (ERO) e redução dos níveis de sulfidrilas no grupo IM e IM+C em relação ao grupo SHAM, enquanto os grupos IM+HT e IM+C+HT não foram diferentes do grupo SHAM. Ainda, no grupo IM+C+HT, o co-tratamento apresentou efeito sinérgico na redução dos níveis de ERO e no aumento da razão GSH/GSSG. Conclusão: A coadminsitração do carvedilol e dos HT foi capaz de melhorar o remodelamento ventricular e a função cardíaca após o IAM. Ainda, o carvedilol foi capaz de exercer seu efeito betabloqueador no grupo IM+C+HT, uma vez que reduziu a frequência cardíaca aumentada pelos HT. Além disso, a co-administração apresentou um efeito sinérgico positivo nos parâmetros de estresse oxidativo, especificamente, sobre os níveis de ERO e o balanço redox através da razão GSH/GSSG, dessa forma preservando a homeostase redox do tecido cardíaco. / Introduction: After acute myocardial infarction (AMI), treatment with thyroid hormones (TH) has revealed cardioprotective effects. However, TH causes adrenergic stimulation, which effect increase heart rate and this may contribute to ventricular dysfunction progression after AMI. Meanwhile, the beta-blocker carvedilol is able to block adrenergic stimulation. Aim: To evaluate the effects of TH and carvedilol co-administration on the heart of rats submitted to AMI. In this context, it focused on the effects of this co-administration on ventricular remodeling, cardiac function and oxidative stress. Material and methods: Male Wistar rats were divided in five groups (n=8-10/group): sham (SHAM), infarcted (MI), infarcted+TH (MI+TH), infarcted+carvedilol (MI+C) and infarcted group+C+TH (IM+C+TH). Post-AMI, SHAM and MI groups received saline, and the treated groups received their respective treatments for 12 days by gavage. After this period, the animals were submitted to an echocardiographic evaluation and, later, to the ventricular catheterization. Afterwards, the animals were euthanized for the heart lung and liver collection, for morphometric and biochemical analyzes. Statistical Analysis: One-way ANOVA followed by Student-Newman-Keuls test. Significance level P<0,05. Results: Regarding the morphometric parameters, it was possible to verify cardiac hypertrophy in the treated infarcted groups in relation to the SHAM and MI groups, as well as there was no significant difference between the groups regarding pulmonary and hepatic congestion. In relation to echocardiographic parameters, treated groups showed an increase in systolic posterior wall thickness, ejection fraction and a reduction in wall tension index compared to MI group. MI+C and MI+C+TH groups also presented attenuation of the reduction in the fractional area change and of the increase in the final systolic volume in relation to the MI and MI+TH groups. Regarding the hemodynamic parameters, there was a reduction of the maximum and minimum dP/dt, the left ventricular (LV) systolic pressure and an increase in the final LV diastolic pressure in the MI group compared to SHAM. However, all these parameters were reversed in the treated groups. The heart rate increased in the MI+TH and MI+C+TH groups compared to the other groups, but decreased in the MI+C+TH group compared to the MI+TH group. Regarding the parameters of oxidative stress, there was an increase in the levels of reactive oxygen species (ROS) and reduction of sulfhydryl levels in the MI and MI+C groups compared to the SHAM group, while the MI+TH and MI+C groups were not different from the SHAM group. In addition, in the M+C+TH group, the co-treatment showed a synergic effect in reducing ERO levels and increasing GSH/GSSG ratio. Conclusion: Coadministration of carvedilol and TH was able to improve ventricular remodeling and cardiac function after AMI. In addition, carvedilol was able to exert its betablocking effect in the MI+C+TH group, since it reduced the heart rate increased by TH. In addition, co-administration had a positive synergistic effect on oxidative stress parameters, specifically on ROS levels and redox balance through the GSH/GSSG ratio, thus preserving redox homeostasis of cardiac tissue.
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Associação entre tempestades geomagnéticas e internações por infarto agudo do miocárdio / Association between geomagnetic activity and daily hospitalization by acute myocardial infarction.Andressa Kutschenko 19 December 2012 (has links)
Os diversos fenômenos solares mostram que a sua atividade não é constante, sendo as manchas solares observadas em sua fotosfera um indicador de atividade do Sol. Os números dessas manchas seguem um ciclo de 11 anos que alterna entre máximos e mínimos; quanto maior o número de manchas, maior o número de erupções no Sol. A literatura médica vem mostrando algumas evidências de que a atividade solar possui alguma relação com a predisposição das pessoas a algumas doenças. As tempestades geomagnéticas são associadas a doenças cardiovasculares, mudanças na pressão arterial sistólica, gravidade da crise de enxaqueca, distúrbios psiquiátricos. As condições da atividade geomagnética são classificadas segundo Batista (2003) em uma escala de Calma, Transição, Ativo, Tempestade fraca, Tempestade intensa ou Tempestade muito intensa. No presente projeto de pesquisa, objetiva-se investigar a associação entre atividade geomagnética e internações diárias por infarto nos hospitais de Ribeirão Preto e região, no período de 1998 a 2007. A hipótese em estudo é que em dias de condições de atividade geomagnética muito perturbada, o número médio de internações por doenças isquêmicas do coração é maior. Para a análise dos dados foi utilizado o modelo de regressão de Poisson com função logarítmica com o auxílio do software SAS 9.2, utilizando o procedimento PROC GENMOD. Observa-se que há evidências de associação entre tempestades geomagnéticas e internações por IAM. / Numerous solar phenomena demonstrate that their activities are not continual, and sunspots noticed in their photosphere are considered an indicator by Suns activity. Numbers linked with these sunspots follow an eleven-year cycle, which alternates between high and low, it means, the greater the number of sunspots, the greater the number of Sun eruptions. Medical Literature has produced evidences that solar activity has some association with people predisposing to some diseases. Geomagnetic storms are related with cardiovascular disease, changes in systolic blood pressure, severity and psychiatric disorders. According to Batista (2003), geomagnetic activity conditions are categorized on a scale of Quiet, Transition, Acting, Weak Storm, Intense Storm or Very Intense Storm. This study intends to investigate the association between geomagnetic activity and daily hospitalization by acute myocardial infarction (AMI) in Ribeirão Preto and its region from 1998 to 2007. The hypothesis being studied is that: day which has unquiet geomagnetic condition, the average number of hospitalizations originated by ischemic heart disease is higher. In order to get on with data analysis, it was used Poissons regression model, with logarithmic function through SAS 9.2, using PROC GENMOD procedure. In consequence, it is observed that there are evidences between geomagnetic storms and hospitalizations by AMI.
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Desenvolvimento de uma nova plataforma para detecção de mioglobina empregando ressonância de plásmons de superfície e medidas eletroquímicas / Development of a new platform for detection of myoglobin using surface plasmon resonance and electrochemical measurementsCarvalho, Rita de Cassia Silva 26 July 2016 (has links)
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Previous issue date: 2016-07-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) / Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) / Cardiovascular diseases (CVDs) are considered as an important cause of morbidity and premature mortality worldwide. Rapid diagnosis of CVD is extremely important to ensure the survival of the patient. Myoglobin (Mb), for its low molecular weight is quickly released in the body, resulting in high sensitivity in order to be as valuable biomarker of acute myocardial infarction (AMI). Therefore, this study aims to develop an efficient platform, sensitive and stable for the immobilization of antibodies (Ab) myoglobin applicable to the monitoring of antigens (Ag) myoglobin using surface plasmon resonance (SPR). In this sense, the cyclic voltammetry, differential pulse voltammetry and impedance spectroscopy were used in selfassembled monolayers research (SAMs) simple and mixed acid 11-mercaptoundecanoic (MUA) and 3-mercaptopropionic acid (MPA). The mixed SAM MPA / MUA 3: 1 ratio showed low resistance to charge transfer and high surface coverage. In order to investigate the SAM capacity MPA / MUA opposite the locking Ac-MB were made comparative studies for the evaluation of the interaction of Ac-MB SAM MPA / MUA well as for SAM MPA / MUA modified polyamidoamine dendrimer of generation 5 (G5 PAMAM). Then, after choosing the more sensitive platform made up AC-Mb interaction studies with different concentrations of Ag-Mb (0,001; 0,5; 0,8; 1 and 500 µg.mL-1) through immunoassay in a "sandwich". The three-dimensional structure of the dendrimer PAMAM G5 favored amplification of SPR signal as grants most accessible area for the immobilization of antibody Mb. The sandwich immunoassay amplified the interaction signal Ac / Ag Mb, with significant advantages in sensitivity immunosensor. The results show that it was possible to develop an immunosensor capable of detecting low concentrations (0.00067 μg.mL-1) Ag-Mb. In this sense, the proposed system has great potential alternative to early diagnosis, simple and fast IAM. / As doenças cardiovasculares (DCVs) são consideradas como importante causa de morbidade e mortalidade prematura em todo o mundo. O diagnóstico rápido das DCVs é extremamente importante para garantir a sobrevivência do paciente. A mioglobina (Mb), por seu baixo peso molecular, é rapidamente liberada no organismo, resultando em elevada sensibilidade de forma a se constituir como precioso biomarcador de infarto agudo do miocárdio (IAM). Portanto, este trabalho tem por objetivo o desenvolvimento de uma plataforma eficiente, sensível e estável para a imobilização de anticorpos (Ac) de mioglobina aplicável ao monitoramento de antígenos (Ag) de mioglobina empregando ressonância de plásmons de superfície (SPR). Neste sentido, as técnicas de voltametria cíclica, voltametria de pulso diferencial e impedância eletroquímica foram empregadas na investigação de monocamadas auto-organizadas (SAMs) simples e mistas de ácido 11-mercaptoundecanóico (MUA) e ácido 3-mercaptopropiônico (MPA). A SAM mista MPA/MUA de proporção 3:1 apresentou baixa resistência à transferência de carga e elevada cobertura de superfície. Com o propósito de investigar a capacidade da SAM de MPA/MUA frente à imobilização de Ac-Mb foram feitos estudos comparativos para a avaliação da interação da do Ac-Mb com a SAM de MPA/MUA bem como para a SAM de MPA/MUA modificada com dendrímero de poliamidoamina de geração 5 (PAMAM G5). Em seguida, após a escolha da plataforma mais sensível, fez-se os estudos da interação do Ac-Mb com diferentes concentrações do Ag-Mb (0,001; 0,5; 0,8; 1 e 500 µg mL-1) através de imunoensaio em formato “sanduíche”. A estrutura tridimensional do dendrímero PAMAM G5 favoreceu a amplificação do sinal de SPR, pois concede uma maior área acessível para a imobilização do anticorpo da Mb. O imunoensaio em sanduíche amplificou o sinal de interação Ac/Ag da Mb, apresentando vantagens significativas na sensibilidade do imunossensor. Os resultados mostram que foi possível desenvolver um imunossensor capaz de detectar baixas concentrações (0,00067 µg.mL-1) do Ag-Mb. Neste sentido, o sistema proposto apresenta grande potencial alternativo de diagnóstico precoce, simples e rápido do IAM.
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The Association Between Leapfrog's Healthcare Organizational Grades and 30-Day Mortality RatesArmstrong, Steven Michael 01 January 2019 (has links)
U.S. healthcare consumers have access to various provider ratings from several organizations that are meant to assist in selecting their healthcare providers. Leapfrog Hospital Safety Grades is one such rating system that professes to allow consumers the ability to select the best hospital for their care. However, since consumers ranking mortality risk as their most important concern, it is essential to determine if Leapfrog grades align with consumer expectations. Andersen's Phase-4 behavioral model of healthcare utilization was used as the foundation for understanding healthcare consumer preferences. This study was designed to determine if Leapfrog grades are predictive of CMS 30-day mortality rates for pneumonia, chronic heart failure, and acute myocardial infarction data, while also adjusting for selected organizational descriptors: state of residency, Medicare expansion, safety-net status, ownership type, teaching classification, and number of licensed beds. Linear regression demonstrated that Leapfrog grades are not reliable predictors of the 3 inpatient mortality rates analyzed. The study demonstrated that ownership type was a significant predictor for 2 of the 3 dependent variables. Furthermore, most of the covariates also provided some predictive value for at least 1 of the included outcomes; however, in most cases, the effect (β) was small. This study can help provide positive social change by elucidating that Leapfrog grades are not reliable predictors of patient outcomes for consumers, while also demonstrating that efforts to reduce 30-day mortality rates, especially for pneumonia, can be targeted by selected states, ownership type, and teaching status.
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Development and Testing of a Nurse Practitioner Secondary Prevention Intervention for Patients after Acute Myocardial InfarctionHarbman, Patricia 09 January 2012 (has links)
Patients with acute myocardial infarction (AMI) are at high risk for reinfarction and death, with the highest rate of death and reinfarction occurring within 30 days of AMI. Therapies that have been shown to reduce these risks (secondary prevention) continue to be underutilized. Nurse practitioners are well positioned to provide secondary prevention during and following hospitalization. The purpose of this pilot study was to examine the feasibility, acceptability, and preliminary effects of an NP delivered secondary prevention intervention. The specific objectives were: 1) to describe NP activities when delivering the secondary prevention intervention; 2) to evaluate the effect of the NP intervention on the rate of implementation of evidence-based secondary prevention treatment strategies and the patients’ achievement of secondary prevention target goals; and, 3) to examine the relationship between the NP activities delivering the intervention and secondary prevention goal achievement by patients.
A prospective cohort design was used, in which patients’ achievement of target goals were compared between patients who received secondary prevention care from an NP and those who received usual care. The sample of convenience consisted of 65 patients with AMI. Data on practice activities and implementation of secondary prevention by the NP were collected before discharge from hospital and one week, two weeks, six weeks and 3 months after discharge. Data on patients’ achievement of goals were obtained before discharge from hospital and 3 months after discharge from both groups. This study’s results provide preliminary evidence that an NP delivered secondary prevention intervention, beginning prior to discharge and continuing for three months post myocardial infarction, significantly improves the implementation and uptake of guideline based secondary prevention treatments and risk factor reduction strategies. NP-led interventions such as this warrant replication. The unique contribution of the NP with this patient population is the training and skills needed to deliver all aspects of secondary prevention, including pharmacological and nonpharmacological therapies, without the immediate availability of a physician.
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