Burn Edema Reduction by Methysergide Is Not Due to Control of Regional Vasodilation

To determine the extent to which edema modulation by methysergide is due to a blunting of the regional vasodilator response to scald and/or local reduction of transvascular fluid flux, a canine hind limb lymphatic was cannulated. Femoral blood flow (Qa; ml/min), lymph flow (QL; μl/min/100 g), and lymph-to-plasma protein ratios (CL/CP) were monitored in groups of five dogs before and 4 hr after 5-sec, 100°C foot paw scald; high (1.0 mg/kg) or low (.5 mg/kg) dose of methysergide 30 min before scald. The compression on a clamp placed around the femoral artery in other dogs was adjusted after scald to simulate the blunting effect on Qaobserved in methysergide treated dogs. Hind leg venous pressure was elevated to ≈40 mm Hg before experimentation until steady state QLand (CL/CP)minwere reached. Protein reflection coefficient (σd; 1 − CL/CP) and fluid filtration coefficient (Kf) were calculated. Compared to preburn values, all groups showed significant (P< 0.002, analysis of variance) increases in CL/CPand Kf. Contrasted with the burn only group, methysergide blunted increases in Qa, Kfand paw weight gain in a dose-dependent fashion, with no effect on the reflection coefficient. Compression clamp control of femoral Qacaused no effects on permeability. Methysergide limits burn edema in a dose-related fashion, though not due to a blunting of the regional vasodilator response. Local, not regional, mechanism(s) likely mediate this response.