GLYBENCLAMIDE BLOCKS THE PROTECTIVE BENEFIT OF ISCHEMIC PRECONDITIONING IN A RAT MODEL OF SPINAL CORD ISCHEMIA

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Introduction. Paraplegia is a common and devastating complication after operations on the thoracic aorta. Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, non-injurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We have previously demonstrated that 3 minutes of IPC followed by 30 minutes of reperfusion prior to 12 minutes of aortic occlusion in a rat model of spinal cord ischemia significantly improves neurologic outcome. [1] This protective benefit may be secondary to the activation of ATP dependent potassium channels. We hypothesized that Glybenclamide (GLYB), a specific KATP blocker, would negate the neuroprotective benefit of IPC. Methods. Male Sprague-Dawley rats (n=31) under halothane anesthesia were randomly assigned to one of 4 groups (IPC, Control, GLYB, or Sham). All animals had an intrathecal catheter placed four to seven days prior to surgery, and were neurologically intact at the time of experimentation. Each group received either 3 minutes of spinal cord ischemia via 2FR balloon occlusion of the thoracic aorta (IPC and GLYB) or no occlusion (Control). After 30 minute recovery, the IPC, GLYB, and Control groups had a 12 minute aortic occlusion. All animals had either placebo or GLYB (10-5 M) injected intrathecally 15 minutes prior to the short 3 minute aortic occlusion. The Sham group (n = 4) also received a placebo intrathecal injection and were subjected to the same experimental conditions with no ischemic events. Neurologic function was evaluated over a 7 day post surgical period. Results. After 7 days, the IPC and Sham groups had significantly lower motor deficit scores compared to the Control, p < 0.05. Figure 1Figure 1: Data from the 4 selected motor neurologic tests (Tarlov, righting, placing and inclined plane) are combined for a composite score. A score of 10 would indicate complete motor neurologic deficit, whereas a 0 would indicate a normal animal.Discussion. IPC reduces neurologic injury in a rat model of spinal cord ischemia. The protective benefit of IPC is invoked after a 30 minute reperfusion interval between the preconditioning and the ischemic event. The protective benefit of IPC is attenuated when intrathecal GLYB is injected 15 minutes prior to the ischemic preconditioning. These data suggest that the ischemic preconditioning of the rat spinal cord may work by ATP dependent potassium channels.