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Doctoral Thesis
DOI
10.11606/T.5.2008.tde-12012009-105643
Document
Author
Full name
Ronaldo Arkader
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Okay, Thelma Suely (President)
Carvalho, Werther Brunow de
Damiani, Durval
Kiss, Maria Helena Bittencourt
Troster, Eduardo Juan
Title in Portuguese
Concentrações de adrenomedulina e relações com o eixo hipófise-adrenal e o controle glicêmico de crianças submetidas à cirurgia cardíaca com circulação extracorpórea
Keywords in Portuguese
Adrenomedulina
Circulação extracorpórea
Criança
Insulina
Sistema hipófise-supra-renal
Abstract in Portuguese
Introdução: Adrenomedulina, peptídeo recentemente identificado, atua como mediador em diversos estados fisiológicos e patológicos, sendo expresso em inúmeros tecidos. Níveis elevados de adrenomedulina foram observados em quadros inflamatórios e sépticos, além de atividade inibitória da adrenomedulina sobre a liberação de insulina, o que poderia contribuir para a gênese e manutenção dos quadros hipeglicêmicos, situação comum em pacientes pediátricos internados em unidades de terapia intensiva, tendo sido comprovado que o controle glicêmico melhora o prognóstico nesses pacientes. O objetivo do estudo foi relacionar as concentrações de adrenomedulina com alterações de hormônios do eixo hipófise-adrenal e o controle glicêmico de crianças submetidas à cirurgia cardíaca com circulação extracorpórea (CEC) representando modelo de síndrome da resposta inflamatória sistêmica. Material e métodos: Foram incluídas 20 crianças com idade entre 11-84 meses submetidas à cirurgia cardíaca com CEC. Foram avaliadas concentrações sangüíneas de glicose, insulina, peptídeo-C, cortisol, ACTH, interleucina-6 e adrenomedulina nos tempos pré-CEC, pós-CEC, 1ºPO, 2ºPO e 3ºPO. Os resultados foram expressos em medianas e inter-quartis. Todas crianças receberam antibioticoterapia profilática (Cefuroxima 150mg/kg) e metilprednisolona (30mg/kg) na indução anestésica. Resultados: Adrenomedulina aumentou de 1,13 ng/mL (0.83 1.81) pré- CEC a 3,28 ng/mL (1.82 4.25) no 1ºPO (p=0,0005). A insulina e o peptídeo-C apresentaram queda do tempo pré-CEC ao 1ºPO: 10,9 U/mL (10.5 13.6) a 2,88 U/mL (1.68 3.46) (p= 0,0001) e 1,44 (0.93 2.08) a 0.89 ng/mL (0.58 2.06) (p=0,076), respectivamente. Houve aumento da glicemia de 86,5 mg/dL (67 88) pré-CEC a 169 mg/dL (153 201) no 1ºPO (p=0,0001). Não houve alterações significativas das concentrações de cortisol e ACTH. Após a CEC todas as concentrações de interleucina-6 encontravam-se elevadas retornando aos valores normais no 3ºPO. Houve correlação negativa entre as concentrações de peptídeo-C e de adrenomedulina no 1ºPO (R= - 0,70 - p< 0,0009). Conclusão: os resultados deste estudo indicam que a adrenomedulina possa ter contribuído para a gênese e manutenção da hiperglicemia em pacientes pediátricos com SRIS, agindo por intermédio da redução das concentrações de insulina e do peptídeo-C
Title in English
Adrenomedullin concentration and relationship with pituitayadrenal axis and glicemic control in children after cardiopulmonary bypass
Keywords in English
Adrenomedullin
Child
Extracorporeal circulation
Insulin
Pituitary-adrenal system
Abstract in English
Background: Adrenomedullin (AM), a recently identified vasoactive peptide, is expressed in a large number of tissues and was found to be increased in some pathophysiologic conditions such as sepsis and Systemic Inflammatory Response Syndrome (SIRS). It has been shown that AM inhibits insulin secretion by means of a direct action on pancreatic -cells thus contributing to the genesis and sustaining of hypeglicemia, a common condition in critically ill pediatric patients. Therefore, the strict control of glucose concentrations has proved beneficial and associated to decrement of morbimortality rates in adults and children. The aim of the present study was to monitor serum adrenomedullin concentration in parallel with interleukin-6, plasma glucose, insulin and C-peptide, as well as ACTH and cortisol in pediatric patients submitted to cardiac surgery and cardiopulmonary bypass (CPB) representing a SIRS model. Methods: Twenty children aged 11-84 months who underwent cardiac surgery requiring cardiopulmonary bypass were prospective studied. Blood glucose, insulin, C-peptide, adrenocorticotropic hormone, cortisol, interleukin- 6 and AM were measured immediately before cardiopulmonary bypass (BCPB), immediately after CPB, on the first (POD1), second (POD2) and third days (POD3) after surgery. Data were expressed by median values and inter quartile range. All children received profilatic antibiotic (cefuroxime 150mg/kg) and methylprednisolone (30mg/kg) during induction of anesthesia. Results: Adrenomedullin increased from 1.13 ng/mL (0.83 1.81) BCPB to 3.28 ng/mL (1.82 4.25) in POD1 (p=0.0005). Insulin dropped from 10.9 U/mL (10.5 13.6) BCPB to 2.88 U/mL (1.68 3.46) in POD1 (p=0.0000). C-peptide decreased from 1.44 (0.93 2.08) BCPB to 0.89 ng/mL (0.58 2.06) in POD1 (p=0.076). Glucose increased from 86.5 mg/dL (67 88) BCPB to 169 mg/dL (153 201) in POD1 (p=0.0000). No significant changes were observed in ACTH and cortisol levels. After CPB, IL-6 concentrations of all patients were significantly increased and returned to basal values in POD3 (p=0.0009). There was a negative correlation between C-peptide an adrenomedullin in POD1 (R= - 0.70 - p< 0.0009). Conclusion: Our results indicate that adrenomedullin might be partly responsible for the genesis and sustaining of hyperglycemia in pediatric SIRS patients, by means of the decrement of insulin and C- peptide levels
 
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Publishing Date
2009-01-20
 
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