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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-01022024-171253
Document
Author
Full name
Elson Alberto Fernandes de Araujo Filho
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Carmona, Maria Jose Carvalho (President)
Andrade, Lucia da Conceição
Badessa, Guinther Giroldo
Otsuki, Denise Aya
Title in Portuguese
Efeito do bloqueio do receptor AT1 no desfecho cardiovascular após parada cardiorrespiratória: estudo experimental em ratos
Keywords in Portuguese
Candesartan
Modelos animais
Parada cardíaca
Reanimação cardiopulmonar
Abstract in Portuguese
INTRODUÇÃO: recentemente, o uso de antagonistas dos receptores de angiotensina II tipo AT1 (ATI) mostrou-se benéfico em situações de isquemia/reperfusão (I/R) focal. Porém, em situações de I/R global, como na parada cardiorrespiratória (PCR), pouco se sabe sobre o bloqueio desses receptores. OBJETIVO: avaliar o uso de bloqueadores de receptores AT1 da angiotensina II após a PCR. MÉTODOS: após a aprovação do comitê de ética, ratos foram alocados em quatro grupos: grupo sham (GS) - animais submetidos a intervenções cirúrgicas, sem PCR; grupo controle (GC) - animais submetidos à PCR, seguida por manobras de ressuscitação cardiopulmonar (RCP); grupo AT1 (GAT1) animais submetidos aos procedimentos descritos para o GC, acrescido 0,2 mg/kg de candesartan intravenoso no início da RCP; Grupo Veículo (GV): animais igualmente induzidos à PCR, sendo administrado 0,2 mL/kg de dimetilsulfóxido (DMSO) a 99%, no início da RCP. Analisou-se taxa de retorno à circulação espontânea, sobrevida, variáveis hemodinâmicas, histopatologia e marcadores de lesão tecidual. RESULTADOS: o GAT1, em relação o grupo controle, apresentou maior taxa de retorno da circulação espontânea (RCE), (62,5% vs. 42,1%, IC: 0,016-0,793; p < 0,0001) e de sobrevida (100% vs. 62,5%, IC: 0,014-0,034; p = 0,027). Esses animais também tiveram menos arritmia após 10 minutos de RCE, (10% vs. 62,5%, IC: 0,001-0,043; p = 0,000). A análise histopatológica demostrou menor escore de lesão neuronal e cardíaca no GAT1 em relação GC (p = 0,025 e p = 0,021, respectivamente). Os grupos não apresentaram diferenças quanto ao tempo de PCR, números de doses de adrenalina ou números de desfibrilações. CONCLUSÃO: o bloqueio do receptor AT1 da angiotensina II foi eficaz para proteção contra lesão neuronal e miocárdica após PCR com maiores taxas de RCE e sobrevida
Title in English
Effect of AT1 receptor blockade on cardiovascular outcome after cardiorespiratory arrest: experimental study in rats
Keywords in English
Animals models
Candesartan
Cardiopulmonary resuscitation
Heart arrest
Abstract in English
INTRODUCION: recently, the use of angiotensin II receptor type AT1 (ATI) antagonists has shown to be beneficial in situations of focal ischemia/reperfusion (I/R). However, in situations of global I/R, such as cardiorespiratory arrest (CA), little is known about the blockade of these receptors. OBJECTIVE: to evaluate the use of angiotensin II AT1 receptor blockers after CA. METHODS After ethics committee approval, rats were allocated into four groups: sham group (SG) - animals submitted to surgical interventions, without CA; control group (CG) - animals submitted to CA, followed by cardiopulmonary resuscitation (CPR) maneuvers; group AT1 (GAT1) animals submitted to the procedures described for the CG, plus 0.2 mg/kg of intravenous candesartan at the beginning of CPR; Vehicle Group (VG): animals equally induced to CA, being administered 0.2 mL/kg of 99% dimethylsulfoxide (DMSO) at the beginning of CPR. The rate of return to spontaneous circulation, survival, hemodynamic variables, histopathology, and markers of tissue injury were analyzed. RESULTS: the GAT1, compared to the control group, had a higher rate of return of spontaneous circulation (ROSC), (62.5% vs. 42.1%, CI: 0.016-0.793; p < 0.0001) and survival (100 % vs 62.5%, CI: 0.014-0.034; p = 0.027). These animals also had less arrhythmia after 10 minutes of ROSC, (10% vs. 62.5%, CI: 0.001-0.043; p = 0.000). The histopathological analysis showed a lower score of neuronal and cardiac injury in the GAT1 compared to the CG (p = 0.025 and p = 0.021, respectively). The groups did not show differences regarding CRP time, number of adrenaline doses or number of defibrillations. CONCLUSION: angiotensin II AT1 receptor blockade was effective for protection against neuronal and myocardial injury after CA with higher ROSC and survival rates
 
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Publishing Date
2024-02-19
 
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