Effect of methysergide on the acute lung mechanics response to endotoxin

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Abstract
The effect of the serotonin antagonist methysergide on the acute lung mechanics response to endotoxin in anesthetized, paralyzed, mechanically ventilated dogs was investigated. In 5 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 2nd group of 5 dogs, methysergide (0.25 mg/kg) markedly attenuated 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 3rd group of 5 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, serotonin evidently is not a mediator of the acute lung mechanics response to endotoxin.