(Stroke. 1995;26:1676-1682.)
© 1995 American Heart Association, Inc.
Articles |
PPBP [4-Phenyl-1-(4-phenylbutyl) Piperidine], a Potent 
-Receptor Ligand, Decreases Brain Injury After Transient Focal Ischemia in Cats
From the Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions (H.T., J.R.K., R.C.K., R.J.T.), and the Neuroimaging and Drug Action Section, Division of Intramural Research, National Institute on Drug Abuse (K.H., E.D.L.), Baltimore, Md.
Background and Purpose We tested the hypothesis that
administration of 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), a
potent 
-receptor ligand, during transient focal ischemia
would affect early postischemic brain injury.
Methods Halothane-anesthetized cats underwent left middle cerebral artery occlusion for 90 minutes followed by 4 hours of reperfusion. Control cats received saline (n=10). Experimental cats (2 groups, n=10 per group) were treated with PPBP at a rate of 0.1 µmol/kg per hour (PPBP-0.1) or administered 1 µmol/kg per hour (PPBP-1) intravenously from 75 minutes after initiation of ischemia and continuing during the 4 hours of reperfusion.
Results As measured by the microsphere method, blood flow to the ipsilateral caudate nucleus was decreased similarly in all groups during ischemia. Blood flow to the ipsilateral inferior temporal cortex was decreased during ischemia in all groups but was higher in cats subsequently treated with PPBP at the highest dose, even before drug administration. There was no difference in blood flow to the ipsilateral caudate nucleus or inferior temporal cortex (area of greatest cortical injury) during reperfusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral hemisphere (control, 29±5%; PPBP-0.1, 17±3%; PPBP-1, 6±1% of ipsilateral hemisphere; mean±SEM) and caudate nucleus (control, 49±5%; PPBP-0.1, 39±6%; PPBP-1, 25±5% of ipsilateral caudate nucleus) was less in cats treated with 1 µmol/kg per hour of PPBP compared with cats treated with saline. Cats treated with 0.1 µmol/kg per hour had a 45% smaller hemispheric injury volume than the control group without differences in intraischemic blood flow. Recovery of somatosensory evoked potential amplitude was greater in cats treated with PPBP-1 compared with control (control, 18±11%; PPBP-0.1, 30±14%; PPBP-1, 54±14% of baseline).
Conclusions These data indicate that -receptors may play an
important role in the mechanism of acute injury in both the cortex and
the caudate nucleus after 90 minutes of transient focal
ischemia in the cat. Because PPBP afforded protection when
administered at the end of ischemia and during reperfusion,
-receptors may contribute to the progression of injury in
ischemic border regions.
Key Words: cerebral blood flow • middle cerebral artery occlusion • sigma receptor • evoked potentials, somatosensory • triphenyltetrazolium staining
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