The clinical efficacy of the lazaroid, tirilazad mesylate, a new therapeutic agent for prophylaxis and treatment of endotoxemia, was evaluated in 24 neonatal Holstein calves. Endotoxemia was induced by iv infusion of commercial Escherichia coli lipopolysaccharide (3.25 µg/kg of body weight) over 3 hours. Group-1 calves were given endotoxin alone; group-2 calves were given an infusion of 0.9% sterile saline solution, then were treated with tirilazad mesylate (1.5 mg/kg) 1 hour after the infusion was started. Group-3 calves were treated with tirilazad mesylate 1 hour after the start of the endotoxin infusion, and group-4 calves were given tirilazad mesylate 1 hour before the start of the endotoxin infusion.
Clinical signs of endotoxemia were mitigated by tirilazad mesylate. In addition, tirilazad mesylate protected calves from endotoxin-induced hyperglycemia; treatment after endotoxin infusion decreased the severity of hypoglycemia and prevented lactic acidosis. Treatment with tirilazad mesylate after initiation of endotoxin infusion was as protective as was pretreatment.
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