• Isabelle Chapados, Tze-Fun Lee, Constance L Chik, and Po-Yin Cheung.
• Department of Paediatrics, University of Alberta, Canada.
• Eur. J. Pharmacol. 2011 Feb 10;652(1-3):111-6.

AbstractIn 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.2010 Elsevier B.V. All rights reserved.

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