Effects of dichloroacetate in spinal stroke in the rabbit.
High levels of brain lactate may contribute to cellular death and dysfunction in acute cerebral ischemia. Although sodium dichloroacetate (DCA) has been shown to lower brain lactate in incomplete cerebral ischemia, functional outcome has not been assessed with DCA. We examined the effects of DCA treatment on functional neurologic outcome using a previously developed model for "spinal stroke" in the rabbit. Thirty male New Zealand white rabbits weighing 1.3-2.8 kg were studied. After anesthesia with 15-40 mg/kg pentobarbital IV, a laparotomy was performed and the aorta exposed. A metal clamp was placed on the aorta just distal to the left renal artery for 20 minutes and then removed. The abdominal wound was closed in two layers. Animals then received either 2cc normal saline (n = 15) or 300 mg/kg DCA in 2cc normal saline (n = 15) over 10 minutes. The animals were returned to their cages when awake and were examined at 24 hours, 48 hours, and 72 hours for neurologic assessment. The exams were performed by a blinded examiner who was unaware of the treatment given. A three point ambulatory score (0 = can't walk, 1 = walk but not hop, 2 = hopping) and a two point activity score (0 = inactive, 1 = active) were used. At 24 hours, 67% of the DCA-treated animals were actively moving about compared to only 27% of the controls (P = 0.03; Fisher Exact Test). Ten of fifteen control animals were unable to walk, while only five of fifteen DCA-treated animals were unable to walk (P = 0.07). Sixty percent of the DCA animals were able to hop compared to 27% of controls (P = 0.06). These results suggest that DCA can reduce morbidity from spinal cord ischemia in the rabbit.
D000085:Acetates / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D007773:Lactates / Q000502:physiology; D019344:Lactic Acid; D008297:Male; D009068:Movement; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply; D013118:Spinal Cord Diseases / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
D000085:Acetates; D001786:Blood Glucose; D007773:Lactates; D019344:Lactic Acid; D003999:Dichloroacetic Acid