Effect of Anti-Lipid A Monoclonal Antibody (E5) on Microcirculatory Function during Lipopolysaccharide Shock

Abstract

Early septic shock is characterized by fever, increased cardiac output, decreased systemic vascular resistance, and dilation of higher-order arterioles in peripheral tissues, such as skeletal muscle. We used a rat model of low-dose lipopolysaccharide (LPS) "septic" shock to investigate the potential benefit of an antilipid A monoclonal antibody preparation (E5) on macro- and microcirculatory function. Twenty-five male Sprague-Dawley rats were anesthetized and instrumented for measurement of arterial pressure (AP), heart rate (HR), and cardiac output (CO). The left cremaster muscle of each rat was prepared for in vivo video microscopic examination of changes in third-order arteriolar (A3) diameter and erythrocyte velocity. Rats were randomly assigned to two groups: Group I (n = 13) received E5 vehicle and 200 μg/kg Escherichia coli LPS; Group II (n = 12) received 2 mg/kg E5 iv prior to LPS administration. All variables were recorded at 15-min intervals for 30 min prior to and 150 min following LPS. Microcirculatory recordings were restricted to those rats where arteriolar diameters were 20-40 μm and vessels displayed obvious vasomotion (n = 7/group). Infusion of LPS caused no significant change in AP, an increase in CO by 105 min, an increase in HR by 75 min, an increase in diameter by 75 min, and a decrease in velocity by 165 min (P < 0.01). Pretreatment with E5 inhibited the A3 vasodilation but did not affect the macrocirculatory changes. These data suggest a potential therapeutic role for E5 in ameliorating LPS-induced changes in skeletal muscle microcirculation.