Effect of repeated administration of tirilazad mesylate on healthy and endotoxemic calves: A pilot study

Tirilazad mesylate (TM:U74006F), a nonglucocorticoid 21-aminosteroid (lazaroid), is beneficial in the treatment of experimentally-induced ischemic injury following brain and spinal cord trauma, subarachnoid hemorrhage, hypovolemic shock and endotoxemia. This study investigated the effects of TM following repeated administration in sixteen healthy and endotoxemic calves. Group A calves received TM 3 mg/kg IV; group B calves received Escherichia coli endotoxin in increasing doses (0.1 to 20 mu g/kg IV); group C calves received TM and endotoxin and group D calves received sterile saline (10 mL). Endotoxin, TM and saline were given every eight hours for five days. Mild, transient tachypnea was observed following TM administration. The drug suppressed clinical signs of endotoxemia until larger doses of endotoxin were given. At necropsy no substantial lesions were observed in groups A and D. Groups B and C had lesions consistent with endotoxemia but only group C calves had evidence of abomasal and ruminal ulceration. Although TM may be of benefit in the treatment of endotoxemia, further studies are needed to determine the optimal dosage and potential side effects in the endotoxic bovine neonate.