SYSTEMIC AND MUSCLE OXYGEN-UPTAKE DELIVERY AFTER DOPEXAMINE INFUSION IN ENDOTOXIC DOGS

Background and Methods: This study was designed to test whether dopexamine, a dopaminergic and beta-2-adrenergic agonist, would a) increase systemic oxygen delivery (Do2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen. There were three treatment groups (n = 6 in each group): control, endotoxin alone (E) 4 mg/ kg iv, and endotoxin + dopexamine (E + D) 12 mu-g/kg.min. Data were analyzed between and within groups by split-plot analysis of variance with significance of identified differences tested post hoc by Duncan's multiple range test. Donor RBC and dextran were used after endotoxin to maintain adequate perfusion pressures, with Hct kept near 40%. Blood flow to left hindlimb muscles was decreased in controlled steps of 15 min each after stabilization. Results: In E group, cardiac output (Qt), mean arterial pressure (MAP), systemic Do2, and oxygen uptake (Vo2) decreased despite blood volume expansion. In E + D group with similar volume expansion, dopexamine maintained Qt, systemic Do2, and Vo2 near the control levels, although MAP and systemic vascular resistance were reduced. In comparison with control subjects, endotoxin increased critical Do2 in the isolated limb muscles from 4.6 to 7.mL/kg.min and decreased critical oxygen extraction from 81% to 68%. The pressure/flow relationship in the limb became flattened, indicating loss of vascular reactivity. In the E + D group, there was no further change in the pressure/flow curve nor in the critical oxygen extraction level. Conclusions: Dopexamine provided hemodynamic support for endotoxic dogs, thereby increasing total DO2 and VO2, while not altering oxygen extraction in the muscle.