CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O acidente vascular cerebral, doenÃa incapacitante e terceira causa de morte em paÃses desenvolvidos à caracterizada pela interrupÃÃo ou reduÃÃo do fluxo sangÃÃneo para o cÃrebro capaz de causar alteraÃÃo na funÃÃo cerebral. Sabe-se que o receptor A1 da adenosina possui um papel chave na neuroproteÃÃo devido à diminuiÃÃo da liberaÃÃo de glutamato e hiperpolarizaÃÃo neuronal. O objetivo desse trabalho foi determinar os efeitos do prÃ-condicionamento por estresse de contensÃo em ratos submetidos à isquemia cerebral transitÃria (ICT) por oclusÃo bilateral das carÃtidas e a participaÃÃo dos receptores A1 da adenosina nesse processo. Inicialmente, ratos Wistar machos, entre 200-240g, foram submetidos ao estresse de contensÃo (ST) em cilindros por 2h e imediatamente depois submetidos à ICT pela oclusÃo de ambas as artÃrias carÃtidas durante 30min. Um dos grupos dos animais foi prÃ-tratado com o antagonista do receptor A1 da adenosina, DPCPX, antes do estresse de contensÃo nas doses de 0,1mg/kg ou 1mg/kg. A temperatura retal foi monitorada e mantida a 37ÂC atravÃs de uma luz incandescente. Vinte e quatro horas depois do tÃrmino da ICT os animais foram sacrificados, tiveram seus cÃrebros dissecados, seccionados e imersos em soluÃÃo de Cloreto de 2,3,5-Trifeniltetrazol (TTC) a 1% por 30 min. para analise da viabilidade do tecido cerebral. Os testes comportamentais foram efetuados 72h apÃs a ICT e consistiram em Teste do Campo Aberto para a atividade locomotora, Labirinto em Y para a memÃria operacional ou de procedimento e Esquiva Passiva para aferiÃÃo da memÃria aversiva de curta e longa duraÃÃo. Os animais submetidos à ICT tiveram dano no tecido cerebral (FO= 10,36  0,75%; ISQ= 18,52  2,62%) alÃm de diminuiÃÃo no comportamento exploratÃrio de rearing (no de eventos: FO= 5,00 1,23; ISQ= 1,50  0,72) e dÃficit da memÃria aversiva de longa duraÃÃo (FO= 271,2  17,61s; ISQ= 108,4 67,64s). Nenhuma diferenÃa significativa foi encontrada no nÃmero de cruzamentos em Campo Aberto (FO= 15,71 2,02; ISQ= 11,00 2,13), na memÃria de procedimento (FO= 70,16  5,77; ISQ= 71,37  7,94), ou na memÃria aversiva de curta duraÃÃo (FO= 145,9  42,75; ISQ= 113,1  64,97).Os animais prÃ-condicionados por estresse tiveram uma reduÃÃo na taxa de infarto cerebral (FO= 10,36  0,75%; ISQ= 18,52  2,62%; ISQ+ST= 12,59  0,87%) e um retorno aos nÃveis normais do comportamento de rearing observado no teste do campo aberto (FO= 5,00 1,23; ISQ= 1,50 0,72; ISQ+ST= 6,091 1,443). No teste de esquiva passiva, observamos uma tendÃncia à melhora da memÃria aversiva de longa duraÃÃo (FO= 271,2  17,61s; ISQ= 108,4 67,64s; ISQ+ST= 156,1Â45,81s). Quando tratados com o DPCPX na dose de 1mg/kg, os animais tiveram um bloqueio da neuroproteÃÃo obtida com o prÃ-condicionamento (ISQ= 18,52  2,62%; ISQ+ST= 12,59  0,87%; ISQ+ST+DPCPX 1= 19,95  3,38%), aumento no nÃmero de rearings que havia sido normalizada pela contensÃo (ISQ= 1,50 0,72; ISQ+ST= 6,091 1,443; ISQ+ST+DPCPX 1= 3,20 0,90) e uma tendÃncia à reversÃo dos efeitos do prÃ-condicionamento na memÃria aversiva de longa duraÃÃo (ISQ= 108,4 67,64s; ISQ+ST= 156,1Â45,81s; ISQ+ST+DPCPX 1= 88,61 38,83s). O estresse de contensÃo conferiu neuroproteÃÃo aos animais submetidos à ICT e tal neuroproteÃÃo foi perdida pelo tratamento prÃvio com DPCPX. Esses achados apontam para a participaÃÃo do receptor A1 da adenosina na proteÃÃo conferida por estresse de contensÃo por mecanismos que ainda precisam ser esclarecidos. / Stroke,as disabling disease and as third cause death in developed countries, is characterized for the interruption of cerebral blood flow capable to cause alteration on brain functions. It is well established that the activation of A1 adenosine receptor confers neuroprotection against acute noxious brains stimuli. The aim of this study was to investigate the effects of preconditionnement by restraint stress on rats subjected to transient cerebral ischemia (TCI) and the participation of A1 receptor in this process. Firstly, Wistar male rats weighing 200-240g were exposed to immobilisation stress for 2 hours followed to TCI by occlusion of both carotid arteries for 30 minutes. Group of animals were pretreated with A1 receptor antagonist DPCPX (0,1mg/kg or 1 mg/kg. i.p.) before immobilisation stress. Retal temperature was monitored and 37ÂC were maintened during cirurgical procedure using a heating light. Infarct size was determined by TTC staining 24h after TCI and the behavioral tests were performed after 72 hours. Open field test were used to assess locomotor activity, Y-maze test for working memory and passive avoidance test to aversive short and long term memory evaluation. Our results showed that TCI caused damage on brain tissue (sham operated= 10.36  0.75%; ISC= 18.52  2.62%), decreased the vertical exploratory behavior (number of events: sham= 5.00  1.23; ISC= 1.50  0.72) and deficit on long term aversive memory (sham= 271.2  17.61s; ISC= 108.4  67.64s). No differences were found on the crossing behavior (sham= 15.71  2.02; ISC= 11.00  2.13), working memory (sham= 70.16  5.77; ISC= 71.37  7.94) neither short term memory (sham= 145.9  42.75; ISC= 113.1  64.97). The infarct volume rates on restraint stress (RS) group were significantly less than ischemic (ISC) group (sham= 10.36  0.75%; ISC= 18.52  2.62%; RS= 12.59  0.87%) while the number of rearing were significantly higher (sham= 5.00 1.23; ISC= 1.50 0.72; RS= 6.091 1.443). On the passive avoidance test, restraint stress tend to impair the ischemic damage on the long term memory (sham= 271.2  17.61s; ISC= 108.4  67.64s; RS= 156.1  45.81s). When treated with DPCPX (1mg/kg) the infarct size show an increase (ISC= 18.52  2.62%; RS = 12.59  0.87%; DPCPX= 19.95  3.38%) suggesting a blockade of neuroprotection action achieved by restraint stress. DPCPX also decreased the number of rearing on the open field test (ISC= 1.50  0.72; RS= 6.091 1.443; DPCPX = 3.20  0.90) and tend to reverse the improvement of long term aversive memory accessed by restraint stress (ISC= 108.4  67.64s; RS= 156.1  45.81s; DPCPX 1= 88.61 38.83s). This work showed a neuroprotection of pre conditioning restraint stress against cerebral ischemia and the blockade of this action by a previously administration of DPCPX, A1 adenosine antagonist. These findings point to the involvement of the A1 adenosine receptor in the protection conferred by restraint stress by mechanisms that still need to be clarified.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Cerebral ischemia is defined as a decrease in blood flow to the brain. It is most often caused by obstruction of a cerebral blood vessel, and is recognized by the World Health Organization as the leading cause of serious adult disability and one of the top three causes of adult death worldwide. Most survivors demonstrate partial restitution of function over time, but the underlying recovery mechanism(s) remain unclear especially in a subset of patients with persistent neurological morbidities despite normal-appearing brain on neuroimaging. The optimal way to understand any human disease state is via clinical studies. Unfortunately, well-controlled experiments in humans are difficult due to small patient populations, the presence of numerous confounding variables, and ethical issues associated with invasive or discomforting experimental procedures. Anesthetized animal models of cerebral ischemia afford a means of avoiding the above difficulties. However, anesthesia and physiological perturbations that occasionally follow brain ischemia may affect the reliability of certain tools used to study this disease, such as functional magnetic resonance imaging (fMRI). Therefore, the central goals of this thesis were: 1) to evaluate the feasibility of performing fMRI in anesthetized and awake animals, 2) to assess fMRI responses under various perturbations of cerebral perfusion and tissue oxygenation in order to identify key factors that may modulate functional signal changes following ischemia, and 3) to utilize fMRI, behavioral tests and histology in an anesthetized animal model of transient focal cerebral ischemia to explore postischemic changes in brain pathology/function and how they relate to changes in behavior. In the first study of this dissertation, I report the evaluation of fMRI responses in anesthetized and awake animals. Anesthesia is frequently used in animal models of cerebral ischemia, but is known to alter brain perfusion and metabolism which may, in turn, affect fMRI responsivity. Perfusion-based fMRI was used to evaluate cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) responses to hypercapnia in awake and isoflurane-anesthetized rats. Hypercapnia produced significant CBF and BOLD fMRI signal changes throughout the cerebrum in awake and isoflurane-anesthetized groups. These results show that perfusion-based fMRI can successfully detect stimulus-evoked hemodynamic changes in the brains of both conscious and isoflurane-anesthetized animals. The second study of this dissertation: 1) investigates the effects of alterations in cerebral perfusion and oxygenation on fMRI signal changes, and 2) examines the self-consistency of an imaging-based formalism for the calculation of the cerebral metabolic rate of oxygen (CMRO2). Functional MRI responses to a stimulus can be described in terms of relative or absolute signal change. A relative fMRI response is defined as a percent-change relative to its own respective baseline value. An absolute fMRI response is defined as a quantitative change relative to a single fixed baseline value that serves as a control. Thus, an absolute fMRI signal change is largely independent of the baseline state and may more accurately index brain activity when baseline fMRI signals change significantly over time due to, for example, hemodynamic-metabolic disturbances that occur during and/or after brain ischemia. To address these issues, the effects of inspired hypoxic, normoxic, hyperoxic, and hypercapnic gases on baseline and forepaw stimulation-evoked changes in BOLD and CBF fMRI signals were examined in isoflurane-anesthetized rats. Relative fMRI responses to forepaw stimulation varied-whereas. absolute responses were similar--across gas conditions. These results demonstrate that absolute measurements of fMRI signal change may lend a more accurate measure of brain activity during states of altered basal physiology as well as support the self-consistency of the imaging-based CMRO2 formalism under these conditions. The third and last study of this dissertation utilized multimodal MRI, behavioral tests, and histology at acute to chronic periods following transient middle cerebral artery occlusion (tMCAO) in the rat to examine the evolution of pathological, functional, and behavioral parameters following transient focal cerebral ischemia. MRI was used to track the evolution of brain pathology and function following cerebral ischemia, and it was found that the cerebral sensorimotor network, critical for sensory and motor behavioral functions, showed profoundly abnormal signal changes that required up to one day to normalize. Adhesive removal, forepaw placement and beam-walk behavioral tests demonstrated sensorimotor dysfunctions that gradually improved but remained long after the recovery of MRI parameters. Postmortem histology confirmed the presence of selective neural cell death within the sensorimotor network at time points when behavior was abnormal. These results suggest that subtle postischemic pathological changes in the brain undetectable by MRI may be responsible for persistent behavioral deficits-a finding which may be relevant to a clinical subset of patients with persistent neurological morbidities despite negative MRI results following cerebral ischemia.

Introdução: O antecedente de AVCI e/ou AIT está presente em 5% dos pacientes com coronariopatia aguda e em até 17% dos pacientes com coronariopatia crônica. Esta população apresenta elevado risco para eventos cardiovasculares, assim como para desfechos hemorrágicos maiores (principalmente quando em uso de tratamento antitrombótico). A agregabilidade plaquetária apresenta papel fundamental no balanço isquêmico/hemorrágico; entretanto, esse mecanismo é pouco estudado em pacientes com evento cérebro vascular isquêmico prévio. O principal objetivo desse estudo é avaliar se pacientes com DAC e AVCI/ AIT prévio exibem alterações na agregabilidade plaquetária que justifiquem o risco aumentado para sangramento nesses indivíduos. Casuística e Métodos: Entre janeiro de 2013 e abril de 2015, 140 pacientes foram selecionados nos bancos de dados da unidade coronária e do serviço de cirurgia cardíaca do InCor- HCFMUSP. Critérios de inclusão: coronariopatia aguda prévia (há mais de 12 meses), antecedente de AVCI/AIT (anterior ao episódio de coronariopatia aguda), uso crônico de AAS e assinatura do Termo de Consentimento Livre e Esclarecido. Critérios de exclusão: AVCH prévio, uso de antiagregação plaquetária dupla ou anti-inflamatórios não esteroidais, trombofilia ou coagulopatia conhecida, trombocitopenia ou trombocitose, angioplastia ou cirurgia cardíaca nos últimos 6 meses, disfunção renal grave ou qualquer doença terminal. Desenho do estudo: Estudo de caso e controle (1:1), com os grupos caso (AVCI/AIT prévio) e controle (sem AVCI/AIT prévio) pareados por sexo, idade, tipo de coronariopatia aguda e tempo entre a coronariopatia aguda e a inclusão no estudo. A agregabilidade plaquetária foi mensurada pelo VerifyNow Aspirin®, VerifyNow P2Y12®, Agregometria óptica com agonista ADP, Agregometria óptica com agonista adrenalina e tromboelastrografia (Reorox®). Resultados: Os grupos controle (n=70) e caso (n=70), estavam bem pareados em relação à maioria das variáveis analisadas. A idade média da população global foi de 66 anos, 73% apresentavam IAM prévio, e o tempo médio entre o episódio de coronariopatia aguda e a inclusão no presente estudo foi de 5,31 anos. No momento da avaliação os pacientes do grupo caso apresentavam valores mais elevados de pressão arterial sistólica (135,84 ± 16,09 vs 123,68 ± 16,11mmHg, p < 0,001), embora esse grupo utilizasse maior número de antihipertensivos (2,37 ± 1,09 vs 3,0 ± 1,23, p=0,006). Em relação a variáveis metabólicas, o perfil lipídico não presentou diferença significativa entre os grupos, entretanto o grupo caso apresentou maiores valores de creatinina (1,24 ± 0,35 vs 1,11 ± 0,27 mg/dL, p=0,037) e também de glicemia de jejum (116,16 ± 32,03 vs 134,88 ± 57,58 mg/dL, p=0,031). No que se refere à meta principal do estudo, a agregabilidade plaquetária foi similar nos dois grupos por todos os métodos utilizados: VerifyNow Aspirin® (525,00 ± 79,78 vs 530,35 ± 83,81 ARU nos grupos caso e controle, respectivamente, p=0,7), VerifyNow P2Y12® (262,14 ± 43,03 vs 251,74 ± 43,72 PRU, p=0,21), Agregometria óptica com agonista ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Agregometria óptica com agonista adrenalina (49,01± 23,93% vs 49,34 ± 21,7, p=0,77), e tromboelastografia (Firmeza máxima do coágulo: 2,136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusão: Em pacientes com doença arterial coronária crônica a agregabilidade plaquetária foi similar nos indivíduos com ou sem AVCI/AIT. Esses resultados apontam para que outros mecanismos sejam responsáveis pelo elevado risco hemorrágico dessa população / Background: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 5% of patients with acute coronary syndrome (ACS) and in 17% of patients with stable atherosclerotic disease (CAD). This population has a higher risk for major cardiovascular events and an increased incidence of major hemorrhagic outcomes when subjected to modern antithrombotic regimens, Platelet aggregability have key role in \"ischemic-hemorrhagic\" balance, however, these factors are little known in the population with prior cerebrovascular event. The aim of this study is to evaluate whether patients with coronary artery disease and previous IS/ TIA exhibit alterations in platelet aggregation, justifying the increased bleeding risk of these individuals. Methods: Between January 2013 and April 2015, 140 participants were selected in the coronary care unit and cardiac surgery service databank. Inclusion criteria: prior ACS (over 12 months), history of IS/ TIA previous to ACS, chronic use of aspirin since ACS and agreement to the consent form. Exclusion criteria: prior hemorrhagic stroke, current dual antiplatelet therapy or anti-inflammatory non-steroidal, any thrombophilia or coagulopathy, thrombocytopenia, thrombocytosis, PCI or CABG in the last 6 months, severe renal impairment and any terminal illness. Study design: Case-control study (1:1), case group (previous IS/TIA) and control group (without previous IS/TIA) matched for sex, age, type of previous ACS, time between ACS and inclusion in the study. Platelet aggregation was assessed by VerifyNow Aspirin®, VerifyNow P2Y12®, Light transmission aggregometry aggonist with agonists adrenaline, Light transmission aggregometry aggonist with ADP, and thromboelastography (Reorox®). Results: The control group (n=70) and case group (n=70), were well matched. The mean age was 63 years, about 73% presented previous AMI and the index ACS occurred 5,31 years before study inclusion. At the evaluation day patients in the case group presented higher SBP levels (135.84 ± 16.09 vs 123.68 ± 16.11 mmHg, p < 0,001), although this group were using more antihypertensive medications (2.37 ± 1.09 vs 3.0 ± 1.23, p=0,006). In relation to metabolic profile, lipid profile did not presented diferences, however, case group presented higher values for creatinine (1.24 ± 0.35 vs 1.11 ± 0.27 mg/dL, p=0.037) and also presented higher values for fasting glucose.(116.16 ± 32.03 vs 134.88 ± 57.58 mg/dL, p=0.031) Platelet aggregation was statistically similar in both groups: VerifyNow Aspirin® (525.00 ± 79.78 vs 530.35 ± 83.81 ARU, p=0.7), VerifyNow P2Y12® (262.14 ± 43.03 vs 251.74 ± 43.72 PRU, p=0.21), Light transmission aggregometry aggonist with agonists ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Light transmission aggregometry aggonist with adrenaline (49,01 ± 23,93% vs 49,34 ± 21,7, p=0,77) and thromboelastography (maximum clot firmness: 2.136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusion: Platlet aggregability is similar in CAD patients with or without previous IS/TIA and this results point at other reasons to justify the high risk for bleeding in this patients

Introdução: O antecedente de AVCI e/ou AIT está presente em 5% dos pacientes com coronariopatia aguda e em até 17% dos pacientes com coronariopatia crônica. Esta população apresenta elevado risco para eventos cardiovasculares, assim como para desfechos hemorrágicos maiores (principalmente quando em uso de tratamento antitrombótico). A agregabilidade plaquetária apresenta papel fundamental no balanço isquêmico/hemorrágico; entretanto, esse mecanismo é pouco estudado em pacientes com evento cérebro vascular isquêmico prévio. O principal objetivo desse estudo é avaliar se pacientes com DAC e AVCI/ AIT prévio exibem alterações na agregabilidade plaquetária que justifiquem o risco aumentado para sangramento nesses indivíduos. Casuística e Métodos: Entre janeiro de 2013 e abril de 2015, 140 pacientes foram selecionados nos bancos de dados da unidade coronária e do serviço de cirurgia cardíaca do InCor- HCFMUSP. Critérios de inclusão: coronariopatia aguda prévia (há mais de 12 meses), antecedente de AVCI/AIT (anterior ao episódio de coronariopatia aguda), uso crônico de AAS e assinatura do Termo de Consentimento Livre e Esclarecido. Critérios de exclusão: AVCH prévio, uso de antiagregação plaquetária dupla ou anti-inflamatórios não esteroidais, trombofilia ou coagulopatia conhecida, trombocitopenia ou trombocitose, angioplastia ou cirurgia cardíaca nos últimos 6 meses, disfunção renal grave ou qualquer doença terminal. Desenho do estudo: Estudo de caso e controle (1:1), com os grupos caso (AVCI/AIT prévio) e controle (sem AVCI/AIT prévio) pareados por sexo, idade, tipo de coronariopatia aguda e tempo entre a coronariopatia aguda e a inclusão no estudo. A agregabilidade plaquetária foi mensurada pelo VerifyNow Aspirin®, VerifyNow P2Y12®, Agregometria óptica com agonista ADP, Agregometria óptica com agonista adrenalina e tromboelastrografia (Reorox®). Resultados: Os grupos controle (n=70) e caso (n=70), estavam bem pareados em relação à maioria das variáveis analisadas. A idade média da população global foi de 66 anos, 73% apresentavam IAM prévio, e o tempo médio entre o episódio de coronariopatia aguda e a inclusão no presente estudo foi de 5,31 anos. No momento da avaliação os pacientes do grupo caso apresentavam valores mais elevados de pressão arterial sistólica (135,84 ± 16,09 vs 123,68 ± 16,11mmHg, p < 0,001), embora esse grupo utilizasse maior número de antihipertensivos (2,37 ± 1,09 vs 3,0 ± 1,23, p=0,006). Em relação a variáveis metabólicas, o perfil lipídico não presentou diferença significativa entre os grupos, entretanto o grupo caso apresentou maiores valores de creatinina (1,24 ± 0,35 vs 1,11 ± 0,27 mg/dL, p=0,037) e também de glicemia de jejum (116,16 ± 32,03 vs 134,88 ± 57,58 mg/dL, p=0,031). No que se refere à meta principal do estudo, a agregabilidade plaquetária foi similar nos dois grupos por todos os métodos utilizados: VerifyNow Aspirin® (525,00 ± 79,78 vs 530,35 ± 83,81 ARU nos grupos caso e controle, respectivamente, p=0,7), VerifyNow P2Y12® (262,14 ± 43,03 vs 251,74 ± 43,72 PRU, p=0,21), Agregometria óptica com agonista ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Agregometria óptica com agonista adrenalina (49,01± 23,93% vs 49,34 ± 21,7, p=0,77), e tromboelastografia (Firmeza máxima do coágulo: 2,136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusão: Em pacientes com doença arterial coronária crônica a agregabilidade plaquetária foi similar nos indivíduos com ou sem AVCI/AIT. Esses resultados apontam para que outros mecanismos sejam responsáveis pelo elevado risco hemorrágico dessa população / Background: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 5% of patients with acute coronary syndrome (ACS) and in 17% of patients with stable atherosclerotic disease (CAD). This population has a higher risk for major cardiovascular events and an increased incidence of major hemorrhagic outcomes when subjected to modern antithrombotic regimens, Platelet aggregability have key role in \"ischemic-hemorrhagic\" balance, however, these factors are little known in the population with prior cerebrovascular event. The aim of this study is to evaluate whether patients with coronary artery disease and previous IS/ TIA exhibit alterations in platelet aggregation, justifying the increased bleeding risk of these individuals. Methods: Between January 2013 and April 2015, 140 participants were selected in the coronary care unit and cardiac surgery service databank. Inclusion criteria: prior ACS (over 12 months), history of IS/ TIA previous to ACS, chronic use of aspirin since ACS and agreement to the consent form. Exclusion criteria: prior hemorrhagic stroke, current dual antiplatelet therapy or anti-inflammatory non-steroidal, any thrombophilia or coagulopathy, thrombocytopenia, thrombocytosis, PCI or CABG in the last 6 months, severe renal impairment and any terminal illness. Study design: Case-control study (1:1), case group (previous IS/TIA) and control group (without previous IS/TIA) matched for sex, age, type of previous ACS, time between ACS and inclusion in the study. Platelet aggregation was assessed by VerifyNow Aspirin®, VerifyNow P2Y12®, Light transmission aggregometry aggonist with agonists adrenaline, Light transmission aggregometry aggonist with ADP, and thromboelastography (Reorox®). Results: The control group (n=70) and case group (n=70), were well matched. The mean age was 63 years, about 73% presented previous AMI and the index ACS occurred 5,31 years before study inclusion. At the evaluation day patients in the case group presented higher SBP levels (135.84 ± 16.09 vs 123.68 ± 16.11 mmHg, p < 0,001), although this group were using more antihypertensive medications (2.37 ± 1.09 vs 3.0 ± 1.23, p=0,006). In relation to metabolic profile, lipid profile did not presented diferences, however, case group presented higher values for creatinine (1.24 ± 0.35 vs 1.11 ± 0.27 mg/dL, p=0.037) and also presented higher values for fasting glucose.(116.16 ± 32.03 vs 134.88 ± 57.58 mg/dL, p=0.031) Platelet aggregation was statistically similar in both groups: VerifyNow Aspirin® (525.00 ± 79.78 vs 530.35 ± 83.81 ARU, p=0.7), VerifyNow P2Y12® (262.14 ± 43.03 vs 251.74 ± 43.72 PRU, p=0.21), Light transmission aggregometry aggonist with agonists ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Light transmission aggregometry aggonist with adrenaline (49,01 ± 23,93% vs 49,34 ± 21,7, p=0,77) and thromboelastography (maximum clot firmness: 2.136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusion: Platlet aggregability is similar in CAD patients with or without previous IS/TIA and this results point at other reasons to justify the high risk for bleeding in this patients

<p>Ciljevi: Cilj ove studije je da ispita bezbednost rane karotidne endarterektomije (CEA) u odnosu na odložene CEA nakon akutnog ishemijskog neurolo&scaron;kog deficita (TIA/CVI). Drugi cilj je da istražimo da li postoji razlika u brzini neurolo&scaron;kog oporavka između navedenih grupa. Metode: Ukupno 157 ispitanika u prospektivnoj studiji je praćeno 30 dana postoperativno. Grupa I ili rana CEA, je imala 50 ispitanika operisanih od 3. do 14. dana po TIA/CVI događaju. Grupa II ili odložena CEA, je imala 107 ispitanika operisanih od 15. do 180. dana nakon TIA/CVI. Praćen je proceduralni op&scaron;ti i specifični morbiditet i mortalitet u 30-dnevnom postoperativnom periodu. Rankin skor (mRS) smo koristili za procenu neurolo&scaron;kog invaliditeta. U odnosu na vrednost mRS skora smo formirali dve podgrupe mRS&lt;3 i mRS3. U statističkoj analizi koristili smo Pirsonov hi test, Studentov test, ANOVU analizu varijanse, Boniferonijev test i multiplu analizu varijanse za ponovljena merenja (GLM- general line model), kao i parametarsku i neparametarsku korelaciju i regresiju. Nivo značajnosti je bio 0,05. Rezultati: Prosečna starost ispitanika je bila 66,72 godine uz 66,2% osoba mu&scaron;kog pola. U grupi I je prosečno vreme do intervencije bilo 9,5 dana, a u grupi II 72,22 dana. Grupe su homogene u odnosu na faktore rizika i komorbiditet. Grupa I je imala 54% nestabilnih aterosklerotskih plakova u poređenju sa grupom II gde ih je bilo 31,8% (&chi;2 = 7.084; p &lt; 0.01). U grupi I TIA je imalo 50% ispitanika, a u grupi II CVI nalaza je bilo 68,2% (&chi;2 =4.825; p &lt;0.05). CVI do 1 cm veličine je statistički značajno vi&scaron;e zastupljen u grupi I , a CVI do 2 cm u grupi II (&chi;2 = 6.913; p &lt;0.05). Stopa CVI je u grupi I bila 2.0% a u grupi II je 2.8% (F = 0.083; p &gt; 0.05). Stopa postoperativnog infarkta miokarda (IM) je u grupi I je 2.0% a u grupi II je 1.9%. Stopa specifičnog hirur&scaron;kog morbiditeta je u grupi I 4.0% a u grupi II 3.7%. U grupi I ukupni morbiditet bio 6.0% a u grupi II 7.5%, razlika nije bila statistički značajna (F =0.921; p &gt; 0.05). Mortaliteta u obe grupe nije bilo. CVI/IM/smrt stopa je u grupi I bio 4.0% a u grupi II je bio 4.7% (F = 0.122; p &gt;0.05). Hiperlipidemija je signifikantan faktor rizika za CVI/IM/smrt (&chi;2 = 4.083; p &lt; 0.05). Pobolj&scaron;anje mRS je u grupi I imalo 52%, a u grupi II 31,8% pacijenata (&chi;2 = 5.903; p &lt;0.01). Relativni rizik je 2,4 odnosno toliko puta je veća &scaron;ansa da kod bolesnika dođe do promene mRS ako je bolesnik u grupi I. Pad mRS koji nastupa između trećeg i desetog dana nakon CEA je statistički visoko značajno izraženiji u grupi ranih CEA ( F 3,701 df 1 p=0,029). Kod bolesnika sa TIA u preko 60% slučajeva do&scaron;lo je do pada mRS, a kod onih koji su imali CVI u oko 25.5% (&chi;2 = 18.050; p &lt; 0.01). Kod Rankin skora podgrupe mRS&lt;3 i mRS3 je pad bio značajan i po vremenu (F 18,774; df 6; p=0,000) i po podgrupi ali je daleko brži pad zapažen u podgrupi mRS&lt;3(F 6,010; df 1; p=0,003). Zaključak: Rana CEA je jednako bezbedna kao i odložena CEA u pogledu incidence perioperativnog morbiditeta i mortaliteta. Ranom CEA se postiže znatno brži neurolo&scaron;ki oporavak pacijenata, naročito onih sa TIA i mRS&lt;3 skorom.</p> / <p>Objectives: The aim of this study was to investigate the safety of early carotid endarterectomy (CEA) in relation to the delayed CEA after acute ischemic neurological events (TIA / CVI). The second objective was to investigate whether there is a difference in speed of neurological recovery between these groups. Methods: A total of 157 patients in the prospective study followed 30 days postoperatively. Group I or early CEA, had 50 patients operated from 3 to 14 days after TIA / CVI event. Group II or delayed CEA, had 107 patients operated from 15 to 180 days after the TIA / CVI. Accompanied by the general and specific procedural morbidity and mortality in 30-day postoperative folow up. Rankin score (mRS) were used for evaluation of neurologic disability. In relation to the value of mRS score we formed two subgroups mRS &lt;3 i mRS3. In the statistical analysis we used the Pearson chi test, Student&#39;s test, ANOVA analysis of variance, Boniferony test and multiple analysis of variance for repeated measures (GLM- general line model), as well parametric and nonparametric correlation and regression. The significance level was 0.05. Results: The mean age was 66.72 years with 66.2% of males. In Group I is the average time to intervention was 9.5 days, and in group II 72.22 days. The groups were homogeneous in relation to risk factors and comorbidities. Group I had 54% of unstable atherosclerotic plaques compared with group II, where it was 31.8% (&chi;2 = 7.084; p &lt;0.01). In the group I TIA had 50% of respondents, while in group II CVI was 68.2% (&chi;2 = 4.825; p &lt;0.05). CVI to 1 cm in size were significantly more frequent in the group I, a CVI to 2 cm in group II (&chi;2 = 6.913; p &lt;0.05). CVI rate in the group I was 2.0%, and in group II was 2.8% (F = 0.083, p&gt; 0.05). Postoperative myocardial infarction (MI) in the group I is 2.0%, and in group II was 1.9%. Specific surgical morbidity rate in the group I and 4.0% in the group II 3.7%. In group I total morbidity was 6.0% in group II 7.5%, the difference was not statistically significant (F = 0.921; p&gt; 0.05). Mortality in both groups was not. CVI/IM/death rate in group I was 4.0% in group II was 4.7% (F = 0.122; p&gt; 0.05). Hyperlipidemia is a significant risk factor for CVI/IM/death (&chi;2 = 4.083; p&lt;0.05). Improving mRS in the group I had 52% and in group II 31.8% of patients (&chi;2 = 5.903; p &lt;0.01). The relative risk was 2.4 times as much and is more likely to occur in patients mRS changes if the patient in group I. Improving mRS that occurs between the third and tenth days after CEA was highly statistically significantly greater in the group of early CEA (F 3,701 df 1 p = 0.029). In patients with TIA in 60% of cases there was a decline mRS, and those had CVI in about 25.5% (&chi;2 = 18.050; p &lt;0.01). In Rankin score subgroups mRS &lt;3 i mRS 3 the decline was significant and time (F 18,774; df 6; p =0.000) and in the subgroup but it is far more rapid decline observed in the subgroup mRS &lt;3 (F 6.010; df 1; p = 0.003). Conclusions: Early CEA is as safe as the delayed CEA in respect incidence of perioperative morbidity and mortality. Early CEA is achieved significantly faster recovery of neurological patients, especially those with TIA and mRS &lt;3 compared with delayed CEA.</p>