flunarizine and Paraplegia

Infrarenal aortic occlusion in rabbits to produce paraplegia is possible in large series and can be achieved without any side-effects of anesthetic drugs. This model was tested for its suitability to investigate the use of calcium-channel blockers, which potentially reduce or prevent ischemic spinal cord damage. In a pilot study 26 rabbits were treated with 0.1 mg/kg Flunarizine i.v. prior to occlusion and 38 animals served as control. Groups were compared where the aorta was occluded for 10, 15, 20, 25 or 30 min. No reduction of paraplegia in the Flunarizine groups was observed, apart from in the 15-min occlusion subset: here the number of unaffected animals was significantly greater (p less than 0.05). At histopathological examination the number of ischemic spinal cord segments was reduced (p less than 0.03). It is concluded that Flunarizine could not reduce the cellular damage of the spinal-cord due to complete and global ischemia after an aortic occlusion interval exceeding 15 min. The narrow interval between potential recovery (15 min) and definite paraplegia (20 min) makes this rabbit paraplegia model less appropriate for testing of calcium-channel blockers which are presumed to have a moderate effect on the reduction of spinal cord ischemia.

Topics: Animals; Aorta, Abdominal; Constriction; Disease Models, Animal; Flunarizine; Ischemia; Paraplegia; Rabbits; Spinal Cord; Time Factors

There is a high incidence of paraplegia associated with thoracic aortic cross-clamping, even when cardiopulmonary bypass or shunts are used. In 56 adult baboons, spinal cord blood flow (SCBF), vascular anatomy, and paraplegia rates were evaluated. Tissue blood flow was measured by radioactive microspheres. Various procedures were used to increase SCBF and to prevent ischemia-reperfusion injury. It was found that the rate of paraplegia was inversely correlated with neural tissue ischemia (SCBF) and directly correlated with reperfusion hyperemia. Two methods completely prevented paraplegia. These two methods were a thoracic shunt with occlusion of the infrarenal aorta or cerebrospinal fluid drainage plus intrathecal papaverine injection, both of which were associated with an increased SCBF. Furthermore, papaverine dilated the anterior spinal artery (ASA) (p = 0.007) and increased the blood flow through the lower ASA. Whereas procedures utilizing a calcium channel blocker (flunarizine), allopurinol, superoxide dismutase (SOD), laminectomy alone, and a thoracoabdominal shunt not perfusing the arteria radicularis magna (ARM) all failed to prevent paraplegia, allopurinol (p = 0.026) and SOD (p = 0.004) did prevent gastric stress lesions, indicating that their failure to prevent paraplegia was not due to a lack of activity. Of great clinical interest is that, if a shunt is used and the ARM is perfused, infrarenal aortic cross-clamping increases SCBF, thus preventing paraplegia. Intrathecal application of papaverine proved to be even more effective in increasing SCBF and also completely prevented paraplegia. As this is a safer procedure than the insertion of shunts, this is the method of choice for the prevention of paraplegia associated with thoracic aortic cross-clamping. The preliminary trial using intrathecal papaverine in human beings has thus far shown no adverse side effects from the drug, and no paraplegia has occurred.

Topics: Allopurinol; Animals; Aorta, Thoracic; Calcium Channel Blockers; Cinnarizine; Flunarizine; Hemodynamics; Laminectomy; Papaverine; Papio; Paraplegia; Regional Blood Flow; Spinal Cord; Superoxide Dismutase