SEROTONIN RECEPTORS REGULATE CANINE REGIONAL VASODILATOR RESPONSES TO BURN

Objective: To determine which serotoninergic receptor subtype(s) mediates the regional vasodilator response to scald injury. Design: Prospective, randomized trial. Setting: Microcirculation research laboratory. Subjects: Anesthetized dogs. Interventions: Mechanically ventilated dogs underwent cannulation of a brachial artery and placement of an ultrasonic flow probe around one femoral artery, Ah animals received a 2% to 3% body surface area partial thickness scald injury by immersing the paw ipsilateral to the instrumented femoral artery into 100 degrees C water for 5 secs. In one group of dogs, BMY 7378 (a serotoninergic(1A) receptor antagonist) was given by the peripheral intravenous route before burn. These results were compared with those findings obtained from a group of animals that received a burn only, and groups of animals given a peripheral intravenous injection of methysergide (a serotoninergic receptor antagonist) or ritanserin (a serotoninergic, receptor blocking agent) before burn. Experiments were conducted for two postburn hours. Measurements and Main Results: Burn injury caused a marked and persistent increase in regional (e.g, femoral artery) blood flow, an effect that was significantly blunted by preburn administration of the serotoninergic(2) receptor antagonist, methysergide. Preburn administration of BMY 7378 increased baseline femoral blood flow by 13%, reflecting its known serotonin agonist properties. However, when compared with the mean postscald increases in femoral blood flow over baseline seen in scald only dogs and in animals given the serotoninergic, receptor blocking agent, ritanserin (before scald), the BMY 7378-treated group demonstrated a significant (p < .001 by analysis of variance) 2-hr-postscald blunting of this femoral vasodilator response. Conclusion: These data suggest that serotoninergic(1A)-like receptors play an integral, albeit not an exclusive, role in blood now regulation to the site of burn injury.