Reduction in spinal cord postischemic lactic acidosis and functional improvement with dichloroacetate.
Pyruvate dehydrogenase complex (PDHC) is a major enzyme of glucose metabolism. Dichloroacetate (DCA) is a noncompetitive inhibitor of PDHC kinase, an enzyme that inactivates PDHC. We examined the effects of DCA on extracellular lactate and pyruvate concentration changes and spinal somatosensory evoked potentials (SSEP) in ischemic rabbit spinal cords. In the first group of 26 animals, the aorta was occluded until postsynaptic SSEP waves were completely suppressed for 10 min, a period of ischemia that causes neurologic deficits in 50% of untreated animals. DCA (25 mg/kg) was given to 13 of these animals before ischemia. In the second group of 24 animals, the aorta was occluded until the postsynaptic SSEP waves were absent for 20 min, a period of ischemia that produces paraplegia in 100% of untreated animals. DCA (25 mg/kg) was given to 16 of these animals just before the aortic occlusion was released. After occlusion, extracellular spinal lactate concentrations increased abruptly while pyruvate concentrations fell. Both lactate and pyruvate concentrations reached a plateau during the ischemic period but increased when the aortic balloon was deflated. DCA-treated animals had lower lactate and pyruvate peak concentrations during reperfusion, as well as more rapid and greater recovery of SSEP at 2 h after reperfusion. DCA did not alter spinal metabolism during the ischemia but appeared to produce a more rapid shift to glucose metabolism on reperfusion. Thus, DCA treatment resulted in better electrophysiological recovery after both moderate and severe ischemia, either by reducing lactic acidosis or by increasing the recovery rate of aerobic energy production.
Robertson
C S
CS
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
Goodman
J C
JC
Grossman
R G
RG
Priessman
A
A
D000085:Acetates / Q000627:therapeutic use*; D000140:Acidosis, Lactic / Q000188:drug therapy / Q000209:etiology*; D000818:Animals; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications* / Q000378:metabolism; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology
D000085:Acetates; D003999:Dichloroacetic Acid