The effects of N-G-nitro-L-arginine-methyl ester on neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits

Little is known about the role of nitric oxide in the pathophysiology of sp inal cord ischemia. We evaluated the effects of nitric oxide synthase (NOS) inhibition by N-G-nitro-L-arginine-methyl ester (L-NAME) in rabbits whose abdominal aorta was occluded for 20 min (Experiment 1) or 25 min (Experimen t 2). in Experiment 1, the L-NAME group (n = 6) received 3 mg/kg TV L-NAME, followed by an TV infusion of 3 mg . kg(-1) h(-1) until 6 h after reperfus ion. Ischemia was induced 20 min after the start of L-NAME. The phenylephri ne group (n = 6) received phenylephrine to maintain comparable blood pressu re. The control group (n = 6) received saline. Ln Experiment 2, L-NAME (3 m g/kg IV L-NAME, followed by an nr infusion of 3 mg . kg(-1) h(-1) until 6 h after reperfusion) and phenylephrine groups (n = 6 each) were studied. Isc hemia was induced 100 min after the start of L-NAME. Forty-eight hours afte r reperfusion, hindlimb motor function and histopathology of the spinal cor d were examined. Tn Experiment 1, L-NAME and phenylephrine both improved ne urologic outcome, with higher intraischemic blood pressures than saline. in Experiment 2, L-NAME worsened the neurologic and histopathologic outcome c ompared with phenylephrine. Attenuation of damage by L-NAME in Experiment 1 may be attributable to an intraischemic blood pressure increase. The worse outcome with L-NAME in Experiment 2 suggests that NOS inhibition exacerbat es ischemic spinal cord damage. Implications: Nonselective inhibition of ni tric oxide synthase activity has aggravating effects on the neurologic and histopathologic outcome after transient spinal cord ischemia.