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Unilateral electroconvulsive therapy_in_rabbit_stroke_model1

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Unilateral electroconvulsive therapy_in_rabbit_stroke_model1

  1. 1. Unilateral Electroconvulsive Therapy in Rabbit Stroke Model: Evaluation Using SPECT Deepak Agrawal, NK Gowda*, R Sagar**, PK Yadav***, Departments of Neurosurgery, Nuclear medicine*, Psychiatry** & Experimental Animal Facility*** All India Institute of Medical Sciences, New Delhi, India-110029
  2. 2. Background <ul><li>rCBF Increases following induced seizure </li></ul><ul><li>Sestoft D, Meden P, Hemmingsen R, et al: Disparity in regional cerebral blood flow during electrically induced seizure. Acta Psychiatr Scand 1993;88:140-143. </li></ul>
  3. 3. Hypothesis <ul><li>This increase in rCBF may have a positive effect on the infarct size following stroke </li></ul>
  4. 4. AIMS & OBJECTIVES <ul><li>To evaluate the efficacy of unilateral electroconvulsive therapy (UECT) for cerebral protection following induced stroke in rabbits </li></ul>
  5. 5. Why Rabbit Model <ul><li>Vascular supply & distribution mimics human brain </li></ul><ul><li>Induced strokes are more representative of humans </li></ul>
  6. 6. Why UECT? <ul><li>ECT has been previously shown to improve rCBF </li></ul><ul><li>UECT causes marked improvement in CBF in the ipsilateral hemisphere </li></ul><ul><li>B/L ECT improves perfusion in striatum </li></ul><ul><li>Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA: Does ECT alter brain structure? Am J Psychiatry 1994;151:957-970 . </li></ul>
  7. 7. Materials & Methods <ul><li>Prospective randomized controlled study </li></ul><ul><li>Randomization: computer generated random number method </li></ul><ul><li>Approval was taken from the institutional ethics committee for animal experiments. </li></ul>
  8. 8. Materials & Methods <ul><li>RABBITS </li></ul><ul><li>New Zealand strain </li></ul><ul><li>Weight- 2-3 kg </li></ul><ul><li>Both Male and female animals were used </li></ul>
  9. 9. Materials & Methods <ul><li>Anesthesia </li></ul><ul><li>Pre-anesthetized by 10% ketamine (20 mg/kg) given IM </li></ul><ul><li>Continuous infusion of midazolam 0.2mg/kg and ketamine (0.2 ml/ kg/hour). </li></ul><ul><li>2ml of 0.5% lignocaine was infiltrated S/C </li></ul>
  10. 10. Materials & methods <ul><li>Operative Procedure </li></ul><ul><li>Femoral cut down for IV access </li></ul><ul><li>2cm long incision along ant border of SCM </li></ul><ul><li>Using blunt dissection CCA exposed </li></ul><ul><li>ICA identified & ligated with silk. </li></ul><ul><li>Wound closed </li></ul>
  11. 11. Materials & Methods <ul><li>2 mCi of Tc-99m HMPAO (Amersham, England) was then injected into the femoral vein, 10 minutes after induced stroke (carotid ligature). </li></ul>
  12. 12. Materials & Methods <ul><li>Animal transported to nuclear medicine on a modified trolley, on ventimask and IV. </li></ul><ul><li>Planar and SPECT images of the brain were taken 50 minutes after stroke. </li></ul>
  13. 13. Materials & Methods <ul><li>UECT Group rabbits </li></ul><ul><li>Unilateral Rt ECT was given 75 minutes after the induced stroke. </li></ul>
  14. 14. Materials & Methods <ul><li>ECT Procedure </li></ul><ul><li>Modified Thymatron (TM) DGx, (Somatics LLC, Lake Bluff, IL, USA) ECT machine </li></ul><ul><li>A brief-pulse square wave (0.5ms) & constant current of 0.9 A. </li></ul><ul><li>Stimulus kept at 10% with impedence (resistance) of 800 ohms </li></ul><ul><li>Induced seizure was considered adequate when its duration > 20 sec. </li></ul>
  15. 15. Materials & Methods <ul><li>CONTROL RABBITS </li></ul><ul><li>NO UECT </li></ul>
  16. 16. Materials & Methods <ul><li>Both groups received 6 mCi of Tc-99m HMPAO after 90 minutes of stroke. </li></ul><ul><li>A second set of planar and SPECT images were taken 150 minutes after stroke. </li></ul>
  17. 17. Materials & Methods <ul><li>Relative uptake of the radiotracer in both groups of rabbits was displayed on computer monitor and was analyzed using a graded grey scale. </li></ul><ul><li>Cerebellum was used as reference site (100% maximum value) for all comparisons </li></ul>
  18. 18. Materials & Methods <ul><li>Rabbits sacrificed using high dose of pancuronium and thiopentone given IV. </li></ul>
  19. 19. STUDY DESIGN 5 RABBITS Rt ICA LIGATION SPECT Brain (50 min after stoke) Randomised to UECT Gp (n=3) Randomised to Control Gp (n=2) Rt Sided UECT No ECT REPEAT SPECT (120 min after stroke) ANIMAL SACRIFIED
  20. 20. RESULTS <ul><li>Study terminated prematurely as Ethics committee withdrew approval after 5 rabbits. </li></ul><ul><li>UECT Group – 3 Rabbits </li></ul><ul><li>Control Group- 2 Rabbits </li></ul>
  21. 21. RESULTS <ul><li>The right cerebrum showed decrease uptake of radiotracer compared to left cerebrum in all five rabbits confirming induction of ischemia. </li></ul>
  22. 22. RESULTS <ul><li>UECT Group </li></ul><ul><li>There was improvement in the regional cerebral blood flow on the affected side in all three rabbits </li></ul>
  23. 23. UECT GROUP PRE-UECT POST-UECT
  24. 24. RESULTS <ul><li>Control group </li></ul><ul><li>No control group rabbit showed any improvement in cerebral perfusion on delayed SPECT. </li></ul>
  25. 25. LIMITATIONS <ul><li>No of rabbits studied was small </li></ul><ul><li>Embolic stroke model would have been preferred to carotid ligation </li></ul><ul><li>PET would have been better in imaging the induced stroke </li></ul>
  26. 26. CONCLUSIONS <ul><li>All rabbits receiving UECT had improvement in cerebral perfusion following induced stroke, vis-à-vis the control group. </li></ul>
  27. 27. CONCLUSIONS <ul><li>This study shows that UECT decreases the infarct size and increases rCBF in rabbit stroke model. </li></ul><ul><li>Further studies using a larger sample size will be required for confirmation. </li></ul>
  28. 28. Thank You

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