• A Oldner, M Wanecek, E Weitzberg, M Rundgren, K Alving, J Ullman, and A Rudehill.
• Department of Anesthesiology and Intensive Care, Karolinska Institute, Stockholm, Sweden.
• Shock. 1999 Feb 1;11(2):127-35.

AbstractThe renin angiotensin system is highly activated in shock states and has been suggested to be involved in the pathophysiology of the markedly deteriorated splanchnic circulation seen in septic shock. The purpose of the present study was to elucidate the capability of losartan, a nonpeptide angiotensin II type 1 (AT1) receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxin shock. A total of 20 pigs were anesthetized and catheterized. Central and regional hemodynamics were monitored. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by losartan administration (n = 10) 2 h later. Ten animals receiving endotoxin only served as controls. The experiments were terminated 5 h after onset of endotoxin challenge. Endotoxin infusion induced an hypodynamic shock with a reduction in cardiac index and systemic oxygen delivery. Losartan reduced both systemic vascular resistance and pulmonary capillary wedge pressure while stroke volume was improved. Pulmonary hypertension induced by endotoxin was significantly reduced by losartan without further changes in gas exchange. The profound reduction in gut oxygen delivery in response to endotoxin was counteracted by losartan administration. However, losartan failed to improve the markedly deteriorated intestinal mucosal pH and mucosal-arterial PCO2gap (i.e., difference in intestinal mucosal PCO2 and arterial PCO2). Also the mucosal-portal venous PCO2gap, used as a monitor of the mucosa in relation to the gut as a whole (including the spleen and pancreas), was greatly increased by endotoxemia but unaffected by losartan administration. In summary, although the angiotensin II type 1 receptor antagonist losartan improved gut oxygen delivery and reduced pulmonary hypertension during established endotoxin shock, it had no effect on intestinal mucosal acidosis. These findings suggest contribution of the angiotensin II type 1 receptor to perfusion disturbances, but not to deterioration of intestinal mucosal homeostasis seen during endotoxemia.

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