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Doctoral Thesis
DOI
10.11606/T.5.2017.tde-07032017-164240
Document
Author
Full name
Vinicius Fernando da Luz
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Carmona, Maria Jose Carvalho (President)
Fantoni, Denise Tabacchi
Ferez, David
Mathias, Ligia Andrade da Silva Telles
Otoch, Jose Pinhata
Title in Portuguese
Avaliação do efeito cardioprotetor do fentanil em suínos submetidos a altas doses de epinefrina
Keywords in Portuguese
Citoproteção
Epinefrina
Fentanila
Modelos animais
Precondicionamento isquêmico miocárdico
Suínos
Abstract in Portuguese
INTRODUÇÃO E HIPÓTESE: A epinefrina é um potente vasoconstritor com efeitos inotrópico e arritmogênico, é utilizada em protocolos de reanimação cardiopulmonar e como fármaco de primeira escolha em alguns casos de choque. Contudo, o seu uso pode ser seguido por lesões do miocárdio e disfunção cardíaca. Modelos experimentais têm mostrado efeitos cardioprotetores do fentanil por meio de mecanismos antiarrítmicos e anti-isquêmicos. O objetivo deste estudo foi avaliar o efeito cardioprotetor do fentanil em suínos expostos a altas doses de epinefrina. MÉTODOS: Após aprovação do comitê de ética institucional, 26 porcos Large White e Landrace foram alocados aleatoriamente em três grupos: grupo fentanil (n = 10), no qual os porcos receberam 20 ug/kg de fentanil 5 minutos antes de 5 doses de 20 ug/kg de epinefrina, as quais foram intercaladas por intervalos de 5 minutos entre cada dose; grupo salina (n = 10), no qual os porcos receberam solução salina volume-equivalente ao fentanil 5 minutos antes das 5 doses de epinefrina e grupo Sham (n = 6), que não recebeu fentanil ou epinefrina. Foram coletadas variáveis hemodinâmicas, ecocardiográficas, gasométricas e marcadores cardíacos durante as 6 horas de experimento. Ao final do estudo, o coração e os pulmões dos porcos foram removidos para análise por microscopia óptica, microscopia eletrônica e imuno-histoquímica (caspase-3). Os dados foram analisados usando equações de estimação generalizadas (GEE) e a significância estatística foi estabelecida em p < 0,05. RESULTADOS: Os níveis de troponina-I entre os grupos foram inicialmente equivalentes. Ao final do experimento, foi observado menor nível de troponina-I no grupo fentanil, em comparação com o grupo salina (1,91 ± 1,47 versus 5,44 ± 5,35 ng.ml-1, p = 0,019). Adicionalmente, a microscopia eletrônica e a imunohistoquímica demonstraram menor lesão miocárdica no grupo fentanil. Não houve diferença significativa entre o grupo fentanil e o salina para as variáveis hemodinâmicas, ecocardiográficas e gasométricas. CONCLUSÃO: O fentanil promove cardioproteção aos efeitos de altas doses de epinefrina sem prejudicar o efeito hemodinâmico da mesma
Title in English
Evaluation of the cardioprotective effect of fentanyl in pigs exposed to highdose epinephrine
Keywords in English
Animals
Epinephrine
Fentanyl
Ischemic preconditioning myocardial, Cytoprotection
Swine
Abstract in English
INTRODUCTION AND HYPOTHESIS: Epinephrine is a powerful vasopressor with inotropic and arrhythmogenic effects that is used in cardiopulmonary resuscitation protocols and as first choice drug in some cases of shock. However, its use could be followed by myocardial injury and dysfunction. Experimental models have shown cardioprotective effects of fentanyl through antiarrhythmic and anti-ischaemic mechanisms. The objective of this study was to evaluate the cardioprotective effect of fentanyl on myocardial function in swine exposed to high doses of epinephrine. METHODS: After institutional ethics committee approval, twenty-six Large White and Landrace pigs were allocated randomly into three groups: Fentanyl group (n=10), which received 20ug/kg of fentanyl five minutes before five doses of 20ug/kg of epinephrine interspersed with 5 minute intervals between each dose; Saline group (n=10), which received saline in a volume-equivalent manner of fentanyl five minutes before 20ug/kg of epinephrine doses; and Sham group (n=6), which did not receive fentanyl nor epinephrine. We assessed hemodynamics, transesophageal echocardiography, cardiac markers, and gasometry for 6 h. At the end of the experiment, the heart and lungs were removed for analysis by optical and electron microscopy and immunohistochemical (Caspase-3) assay. Data was analyzed using generalized estimating equations (GEE) and statistical significance was assumed at p < 0.05. RESULTS: Troponin levels among the groups were initially equivalent. Fentanyl group showed lower levels of troponin at the end of the sixth hour compared to the saline group (1.91 ± 1.47 vs. 5.44 ± 5.35 ng.mL-1, p=0.019). There were no significantly difference between fentanyl and saline group for hemodynamic, echocardiographic and gasometrical data. Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. CONCLUSION: We concluded that fentanyl promotes effective cardioprotection to high-dose epinephrine without blunting the hemodynamic effect of epinephrine
 
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Publishing Date
2017-03-07
 
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