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 is chemic injury following brain and spinal cord trauma, subarachnoid hem orrhage, hypovolemic shock and endotoxemia. This study investigated th e effects of TM following repeated administration in sixteen healthy a nd endotoxemic calves. Group A calves received TM 3 mg/kg IV; group B calves received Escherichia call 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 o bserved following TM administration. The drug suppressed clinical sign s of endotoxemia until larger doses of endotoxin were given. At necrop sy no substantial lesions were observed in groups A and D. Groups B an d C had lesions consistent with endotoxemia but only group C calves ha d evidence of abomasal and ruminal ulceration. Although TM may be of b enefit in the treatment of endotoxemia, further studies are needed to determine the optimal dosage and potential side effects in the endotox ic bovine neonate.