Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats

TY - JOUR

T1 - Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats

AU - Schumacher, J

AU - Puchakayala, M R

AU - Binkowski, K

AU - Klotz, K-F

AU - Dendorfer, A

AU - Klotz, K-F

PY - 2006/4

Y1 - 2006/4

N2 - 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 (AT(1)-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 AT(1) and ACE-blockade before acute non-resuscitated 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.

AB - 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 (AT(1)-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 AT(1) and ACE-blockade before acute non-resuscitated 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.

KW - Angiotensin II Type 1 Receptor Blockers

KW - Angiotensin-Converting Enzyme Inhibitors

KW - Animals

KW - Benzimidazoles

KW - Capillary Permeability

KW - Coloring Agents

KW - Enalaprilat

KW - Evans Blue

KW - Extravasation of Diagnostic and Therapeutic Materials

KW - Hemodynamics

KW - Ileum

KW - Kidney

KW - Lactic Acid

KW - Male

KW - Oxygen Consumption

KW - Rats

KW - Rats, Sprague-Dawley

KW - Renin-Angiotensin System

KW - Shock, Hemorrhagic

KW - Tetrazoles

KW - Journal Article

U2 - 10.1093/bja/ael030

DO - 10.1093/bja/ael030

M3 - Article

C2 - 16490762

SN - 0007-0912

VL - 96

SP - 437

EP - 443

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 4

ER -