Introduction
Laser speckle flowmetry allows detailed examination of evolution of focal cortical ischaemia. Using this method, we assessed the contribution of secondary deterioration in perfusion to the evolution of the ischaemic process in the gyrencephalic brain, with special reference to the role of peri-infarct depolarisations.
Methods
In 11 cats anaesthetised with chloralose (60 mg/kg), the cortical territory of the right middle cerebral artery (MCA) was exposed under oil, and the vessel occluded for four hours. Perfusion in the superficial cerebral cortex was imaged at ∼13-sec intervals with laser speckle flowmetry, yielding a signal related to perfusion 1 . Mean grey levels representing perfusion in the core (ectosylvian, EG), intermediate (suprasylvian, SG) and outer penumbral (marginal, MG) gyri were extracted at 15-minute intervals. Entire image sets were reviewed as time lapse videos for evidence of propagating changes in perfusion.
Results
In 7 experiments there was a substantial area of ischaemia after 4 hours (Group 1, Table 1), whereas in the remaining 4 (Group 2) perfusion was close to baseline, having recovered to that level on core and penumbral gyri within 10 minutes of occlusion. Immediate postocclusion perfusion was similar in the 2 groups, but in 5 of Group 1 there was a substantial secondary deterioration in perfusion between 10 and 240 minutes (the remaining 2 achieved little collateral perfusion). One or more spontaneous, sudden reductions in perfusion occurred on SG in all of these 5 experiments, and propagated in 1,2 or 3 gyri, with a rate characteristic of spreading depression or of peri-infarct depolarisation (PID). In 4 of the 5 studies, they were associated with sustained reductions in perfusion and enlargement of the area of ischaemia. On lateral MG (MCA), changes were transient and often biphasic (reduction, then increase).
Discussion
The incidence of experiments with minimal or no ischaemia (Group 2) at 4 hours (despite an initial effect of occlusion comparable with the lesion group) resembles earlier results in this species 2 . SG and EG were better collateralised at 10 minutes in Group 2, and remained so at 240 min (Table 1). Perfusion fell secondarily in Group 1, especially in EG. These experiments indicate graphically that PIDs are associated with marked, secondary reductions in perfusion in the ischaemic, gyrencephalic brain, in addition to their known adverse metabolic effects. They also show that PIDs are not the only cause of delayed loss of perfusion.
Footnotes
Acknowledgements
This work was carried out in collaboration with the sponsors, Shionogi-GlaxoSmithKline Pharmaceuticals LLC. We thank Andrew Dunn for the speckle imaging software.