unilateral electroconvulsive therapy_in_rabbit_stroke_model1

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

UECT in rabbit stroke model

Background

• rCBF Increases following induced seizure

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.

UECT in rabbit stroke model

Hypothesis

• This increase in rCBF may have a positive effect on the infarct size following stroke

UECT in rabbit stroke model

AIMS & OBJECTIVES

• To evaluate the efficacy of unilateral electroconvulsive therapy (UECT) for cerebral protection following induced stroke in rabbits

UECT in rabbit stroke model

Why Rabbit Model

• Vascular supply & distribution mimics human brain

• Induced strokes are more representative of humans

UECT in rabbit stroke model

Why UECT?

• ECT has been previously shown to improve rCBF

• UECT causes marked improvement in CBF in the ipsilateral hemisphere

• B/L ECT improves perfusion in striatum

Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA: Does ECT

alter brain structure? Am J Psychiatry 1994;151:957-970.

UECT in rabbit stroke model

Materials & Methods

• Prospective randomized controlled study

• Randomization: computer generated random number method

• Approval was taken from the institutional ethics committee for animal experiments.

UECT in rabbit stroke model

Materials & Methods

RABBITS• New Zealand strain• Weight- 2-3 kg• Both Male and female animals were used

UECT in rabbit stroke model

Materials & Methods

Anesthesia• Pre-anesthetized by 10% ketamine (20

mg/kg) given IM• Continuous infusion of midazolam

0.2mg/kg and ketamine (0.2 ml/ kg/hour).• 2ml of 0.5% lignocaine was infiltrated S/C

UECT in rabbit stroke model

Materials & methods

Operative Procedure• Femoral cut down for IV access• 2cm long incision along ant border of SCM• Using blunt dissection CCA exposed• ICA identified & ligated with silk.• Wound closed

UECT in rabbit stroke model

Materials & Methods

• 2 mCi of Tc-99m HMPAO (Amersham, England) was then injected into the femoral vein, 10 minutes after induced stroke (carotid ligature).

UECT in rabbit stroke model

Materials & Methods

• Animal transported to nuclear medicine on a modified trolley, on ventimask and IV.

• Planar and SPECT images of the brain were taken 50 minutes after stroke.

UECT in rabbit stroke model

Materials & Methods

UECT Group rabbits• Unilateral Rt ECT was given 75 minutes

after the induced stroke.

UECT in rabbit stroke model

Materials & MethodsECT Procedure • Modified Thymatron (TM) DGx, (Somatics

LLC, Lake Bluff, IL, USA) ECT machine• A brief-pulse square wave (0.5ms) &

constant current of 0.9 A.• Stimulus kept at 10% with impedence

(resistance) of 800 ohms • Induced seizure was considered adequate

when its duration > 20 sec.

UECT in rabbit stroke model

Materials & Methods

CONTROL RABBITS

• NO UECT

UECT in rabbit stroke model

Materials & Methods

• Both groups received 6 mCi of Tc-99m HMPAO after 90 minutes of stroke.

• A second set of planar and SPECT images were taken 150 minutes after stroke.

UECT in rabbit stroke model

Materials & Methods

• Relative uptake of the radiotracer in both groups of rabbits was displayed on computer monitor and was analyzed using a graded grey scale.

• Cerebellum was used as reference site (100% maximum value) for all comparisons

UECT in rabbit stroke model

Materials & Methods

Rabbits sacrificed using high dose of pancuronium and thiopentone given IV.

UECT in rabbit stroke model

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

UECT in rabbit stroke model

RESULTS

• Study terminated prematurely as Ethics committee withdrew approval after 5 rabbits.

• UECT Group – 3 Rabbits• Control Group- 2 Rabbits

UECT in rabbit stroke model

RESULTS

The right cerebrum showed decrease uptake of radiotracer compared to left cerebrum in all five rabbits confirming induction of ischemia.

UECT in rabbit stroke model

RESULTS

UECT Group

• There was improvement in the regional cerebral blood flow on the affected side in all three rabbits

UECT in rabbit stroke model

UECT GROUP

PRE-UECT POST-UECT

UECT in rabbit stroke model

RESULTS

Control group

• No control group rabbit showed any improvement in cerebral perfusion on delayed SPECT.

UECT in rabbit stroke model

LIMITATIONS

• No of rabbits studied was small• Embolic stroke model would have been

preferred to carotid ligation• PET would have been better in imaging

the induced stroke

UECT in rabbit stroke model

CONCLUSIONS

• All rabbits receiving UECT had improvement in cerebral perfusion following induced stroke, vis-à-vis the control group.

UECT in rabbit stroke model

CONCLUSIONS

• This study shows that UECT decreases the infarct size and increases rCBF in rabbit stroke model.

• Further studies using a larger sample size will be required for confirmation.

UECT in rabbit stroke model

Thank You