Stroke, Vol 24, 1547-1553, Copyright © 1993 by American Heart Association
SH Johnson, JM Kraimer and GM Graeber
BACKGROUND AND PURPOSE: The lipophilic calcium channel antagonist
flunarizine has been demonstrated to be neuroprotective in several models
of cerebral ischemia. Ischemic spinal cord injury may have a similar
pathophysiology and hence may respond in a similar fashion. This study was
designed to investigate the effects of pretreatment with flunarizine on
systemic hemodynamics, spinal cord blood flow, and neurological recovery in
a rabbit model of ischemic spinal cord injury. METHODS: New Zealand White
rabbits were anesthetized with ketamine and xylazine and instrumented for
systemic blood pressure monitoring and spinal cord blood flow measurements
using the microsphere method. After pretreatment with flunarizine or
vehicle, ischemic spinal cord injury was created selectively in the caudal
regions of the spinal cord by cross-clamping the abdominal aorta for a
period of 25 minutes. Spinal cord blood flow was measured before, during,
and 15 minutes after cross- clamp removal. Animals were allowed to recover
and were graded neurologically at 18 and 24 hours after ischemia. RESULTS:
Flunarizine injection was associated with hypotension that was both
transient and dose related. Animals pretreated with flunarizine 0.4 mg/kg
had significantly improved neurological recovery scores at 18 hours after
ischemia (P = .017) compared with vehicle controls. At 24 hours this effect
was lessened (P = .095); however, 60% of flunarizine-treated animals
retained their ability to hop, whereas all of the vehicle- treated animals
were nonambulatory. CONCLUSIONS: Flunarizine has a protective effect on
neurological recovery after experimental ischemic spinal cord injury. The
therapeutic window is narrow, and dosing is limited by untoward
hypotension. The mechanism of protection likely involves inhibition of
pathological cytosolic calcium accumulation rather than a direct effect on
vascular smooth muscle.
ARTICLES
Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits
Division of Surgery, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC.
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