Neurologic deficits after the surgical repair of thoracic and thoracoabdominal
aortic disease are devastating complications. Recently, pharmacologic preconditioning with
potassium channel openers was reported to protect the spinal cord against neurologic injury in a model of
spinal cord ischemia. A novel
benzopyran derivative with an N-
cyanoguanidine group,
KR-31378, has been synthesized as a new therapeutic agent against ischemic injury. In the present study, we evaluated the protective effects of
KR-31378 on spinal cord ischemic injury and compared its neuroprotective activities and hemodynamic stabilities with those of
diazoxide. Thirty-four New Zealand white rabbits were randomly divided into four groups:
ischemia group (n = 10, 25 min of aortic cross-clamping without any intervention),
diazoxide group (n = 8,
diazoxide [5 mg/kg] intravenously 15 min before the 25-min cross-clamping), KR20 group (n = 8,
KR-31378 [20 mg/kg] intravenously 30 min before the 25-min cross-clamping), and the KR50 group (n = 8,
KR-31378 [50 mg/kg] intravenously 30 min before the 25-min cross-clamping). Neurologic functions were evaluated for 72 h postoperatively using modified Tarlov's scores. All rabbits were sacrificed for histopathologic observations after finally scoring neurologic function. All rabbits but three survived. The rest were completely evaluated 72 h postoperatively. Unlike
diazoxide-treated rabbits, KR-31378-treated rabbits showed relatively stable hemodynamics. Tarlov's score outcomes showed a marked improvement in the
diazoxide group, in the KR20 group, and in the KR50 group compared to the
ischemia group (p = .005, .002, and .001, respectively). However, Tarlov's scores in the KR50 group were not significantly different from those of the
diazoxide group. Histopathologic data were not significantly different between the groups, but the degree of degenerative change in motor neurons showed a significant correlation with Tarlov's scores 3 days postoperatively (gamma = -.378, p = .036). Thus, the administration of
KR-31378 before the aortic cross-clamping resulted in a significant improvement in neurologic outcome with stable hemodynamics in this rabbit model.