Weakness and/or paralysis of lower limbs following thoracoabdominal aortic aneurysm surgery result mainly from loss of blood flow (ischemia) to the spinal cord, a consequence of clamping the aorta to prevent bleeding. While severe deficits can be controlled through reduced ischemia time, the mere act of reintroducing blood and oxygen (reperfusion) also causes cellular damage. Ischemia-reperfusion injury exerts its effects on the spinal cord via release of reactive oxygen species, damage to cellular components such as mitochondria, and initiation of cell death.
Dr. Chiming Wei and colleagues from the Department of Surgery at The Johns Hopkins University School of Medicine have specifically targeted ischemia-reperfusion-mediated mitochondrial damage, which directly contributes to cell death. They hypothesized that they could prevent spinal cord injury if they blocked mitochondrial damage with the drug diazoxide, which prevents mitochondrial failure and subsequent cell death.
Using a rabbit model of ischemia-reperfusion injury, Dr. Wei's team demonstrated that administration of diazoxide prevented hind limb paralysis. All animals treated with diazoxide prior to clamping of the aorta retained mobility in their hind limbs, though hopping was impaired, in sharp contrast to complete hind limb paralysis in all untreated animals. Further, mitochondria from spinal cords of diazoxide-treated rabbits displayed considerably less structural damage compared to those of untreated animals. Overall, diazoxide prevented or lessened release of reactive
Contact: Audra Cox
American Journal of Pathology