Effect of methysergide on the acute lung mechanics response to endotoxin

The effect of the serotonin antagonist methysergide on the acute lung mechanics response to endotoxin in anesthetized, paralyzed, mechanically ventilated dogs was investigated. In five dogs given 0.25 mg/kg Escherichia coli endotoxin only, the pulmonary nonelastic resistance (RL) increased to 238% of control and dynamic compliance (CL) decreased to 50% of control. In a second group of five dogs, methysergide (0.25 mg/kg) was shown to markedly attenuate the lung mechanics response to serotonin (0.04 mg/kg), which alone had produced changes in lung mechanics greater than endotoxin. In these same dogs endotoxin administered after injection of methysergide produced an increase in RL to 377% and a decrease in CL to 33% of control. In a third group of five dogs whose lung mechanics response to serotonin was also greater than to endotoxin alone, endotoxin administered after injection of saline produced an increase in RL to 168% and a decrease in CL to 58% of control. Since the response to endotoxin after injection of methysergide exceeded the response after saline, we conclude that serotonin is not a mediator of the acute lung mechanics response to endotoxin.