Adrenergic Mechanisms Contribute to Alterations in Regional Perfusion during Normotensive E. coli Bacteremia

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Abstract
The complex role of adrenergic mechanisms in the pathogenesis of sepsis and shock remains incompletely understood. Recent reports have suggested that adrenergic mechanisms may play an important modulatory role in arachidonate metabolism during early sepsis, specifically in the synthesis of the vasoactive metabolites thromboxane A2 and prostacyclin. The purpose of the present set of experiments was to evaluate the extent to which adrenergic mechanisms contribute to early alterations in regional perfusion during Gram-negative bacteremia, using the mixed alpha adrenergic receptor antagonist phenoxybenzamine hydrochloride. Male Sprague-Dawley rats received a 3-hour continuous intraarterial infusion of either saline (n = 7) or 6.6 .+-. 0.4 .times. 108 live E. coli colony forming units (n = 7), after which regional perfusion was determined using 51Cr-labelled microspheres (16.5 .+-. 0.1 micron). Significant reductions (p < 0.05) in blood flows to the renal, gastric, cecal, pancreatic, and splenic beds, as well as a reduction (p < 0.05) in the calculated portal venous flow, were observed in the bacteremic group while mean arterial blood pressure remained unchanged. Further experiments conducted in 14 rats with preexisting alpha adrenergic receptor blockade revealed relative preservation of renal, gastric, cecal, and portal venous blood flows during bacteremia. These data identify alterations in regional perfusion during early E. coli bacteremia occurring before changes in systemic arterial blood pressure, and indicate that adrenergic mechanisms participate in the modulation of such.