Document Detail

Hydrocortisone administration increases pulmonary artery pressure in asphyxiated newborn piglets reoxygenated with 100% oxygen.
MedLine Citation:
PMID:  21114992     Owner:  NLM     Status:  In-Process    
In severely asphyxiated neonates developing vasopressor-resistant shock, hydrocortisone is commonly used to improve perfusion. However, its acute haemodynamic effects in asphyxiated neonates are largely unknown. In a swine model of neonatal asphyxia, effects of hydrocortisone on systemic and pulmonary circulations were examined. Piglets (1-3d, 1.5-2.4kg) were acutely instrumented to measure heart rate, systemic and pulmonary artery pressures, and pulmonary artery flow. After 2h of normocapnic hypoxia, animals were resuscitated with 100% oxygen for 1h followed by 21% oxygen for 3h. Intravenous hydrocortisone (1mg/kg) or saline was given in a blinded, randomized fashion 2h after reoxygenation (n=6/group). Haemodynamic parameters, blood gases, plasma cortisol, as well as levels of endothelin-1, nitrite/nitrate, nitrotyrosine, matrix metalloproteinases-2 and -9 in the lung were analysed. Severe hypoxia caused metabolic acidosis (mean pH: 6.91-6.97, mean plasma lactate: 17.2-18.3mM), tachycardia and shock. Hydrocortisone did not affect systemic haemodynamics which recovered with reoxygenation, but it increased pulmonary artery pressure at 90-120min after administration (36±3 vs. 27±2 and 26±1mmHg for hypoxia-reoxygenation control and sham-operated piglets, respectively, P<0.05). In the lung tissue, hydrocortisone significantly increased endothelin-1 and nitrite/nitrate levels, but had no effect on nitrotyrosine. Further, it decreased lung matrix metalloproteinase-9, but not matrix metalloproteinase-2, activity, which were both elevated with hypoxia-reoxygenation. It is most likely that the increase in pulmonary artery pressure observed after hydrocortisone treatment was associated with increased endothelin-1 level in the lung. Our findings caution the use of hydrocortisone as a first-intention treatment of shock in asphyxiated neonates.
Isabelle Chapados; Tze-Fun Lee; Constance L Chik; Po-Yin Cheung
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-27
Journal Detail:
Title:  European journal of pharmacology     Volume:  652     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  111-6     Citation Subset:  IM    
Copyright Information:
2010 Elsevier B.V. All rights reserved.
Department of Paediatrics, University of Alberta, Canada.
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Grant Support
//Canadian Institutes of Health Research

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