BJA Advance Access originally published online on February 20, 2006
British Journal of Anaesthesia 2006 96(4):437-443; doi:10.1093/bja/ael030
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Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats
1Department of Anaesthetics, Guy's and St Thomas' NHS Foundation Trust London, UK
2Department of Anaesthetics, University of Luebeck Germany
3Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck Germany
*Corresponding author: Department of Anaesthetics, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. E-mail: jan.schumacher{at}gstt.sthames.nhs.uk
Background. To counteract the contribution of angiotensin II to shock-induced ischaemic organ damage pharmacologic blockade of the renin–angiotensin-system (RAS) is currently under investigation. To evaluate potential side-effects of RAS blockade regarding capillary leak, we studied alterations in microvascular permeability in various organs during haemorrhagic shock (HS) in rats pretreated with candesartan (AT1-receptor antagonism) or enalaprilat (ACE-inhibition).
Methods. Thirty-eight instrumented and anaesthetized animals received either candesartan, enalaprilat or placebo. Within each of the three groups 6–7 animals were exposed to HS and 6 animals of each group served as normovolaemic controls. After 30 min of shock, 50 mg kg–1 Evans blue (EB) was injected i.v. followed by a distribution period of 20 min. Exsanguination was performed with saline, before harvesting organs to quantify albumin-bound EB extravasation.
Results. To reduce cardiac output from 37.5 (1.3) to 20.4 (1.1) ml min–1 [mean (SEM)] in the shock groups, withdrawal of 4.0 (0.25) ml [mean (SEM)] blood was necessary. Simultaneously mean arterial pressure decreased from 77.5 (3.2) to 36.1 (2) mm Hg. Serum lactate increased significantly from 1.3 (0.1) to 3.5 (0.24) mmol litre–1. Treatment with candesartan increased EB extravasation in the kidney in normovolaemic controls. Specific AT1 and ACE-blockade before acute nonresuscitated HS significantly increased EB extravasation in the rat ileum by 53 and 66%, respectively.
Conclusion. This observation of increased microvascular albumin extravasation should be borne in mind for any interventional use of candesartan or enalaprilat during circulatory stress.