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; microliter/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 degrees 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 Qa observed in
methysergide treated dogs. Hind leg venous pressure was elevated to approximately = 40 mm Hg before experimentation until steady state QL and (CL/CP)min were reached.
Protein reflection coefficient (sigma d; 1-C1/ 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/CP and Kf. Contrasted with the
burn only group,
methysergide blunted increases in Qa, Kf and paw
weight gain in a dose-dependent fashion, with no effect on the reflection coefficient. Compression clamp control of femoral Qa caused 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.