Influence of brain injury on opioid-induced pial artery vasodilation. Thorogood, M. C., and W. M. Armstead. Departments of Anesthesia and Pharmacology, The University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399
APStracts 2:0238H, 1995.
The present study was designed to investigate the effect of fluid percussion brain injury on opioid induced pial artery vasodilation in the newborn pig. It has been previously observed that brain injury produces pial artery vasoconstriction associated with elevated CSF opioid levels in the piglet. Additionally, opioids produce pial vasodilation that is attenuated by the NO synthase inhibitor LNA . Anesthetized newborn (1-5 days old) pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Cortical periarachnoid CSF was collected from beneath the window for assay of cGMP. Topical administration of methionine enkephalin, an endogenous m opioid agonist in physiologic and pharmacologic concentrations (10 -10,10-8,10-6M), produced vasodilation that was attenuated following brain injury (7+1 vs 3+1, 1 + 1 vs 5 + 1% and 16 + 1 vs 8 + 1 % for 10-10, 10-8, 10-6M methionine enkephalin before and after injury, respectively, n=5). Methionine enkephalin induced dilation was associated with increased cortical periarachnoid CSF cGMP and these biochemical changes were blunted by brain injury (342 + 12 and 640 + 13 vs 267 + 6 and 321 + 17 fmol/ml for control and methionine enkephalin 10-6M before and after injury respectively, n=5). Leucine enkephalin, an endogenous [delta] agonist (10-10,10-8, 10-6M), induced pial dilation and associated changes in CSF cGMP which were similarly altered by brain injury. In contrast, dynorphin, an endogenous k agonist (10-10,10-8, 10-6M), elicited vasodilation that was reversed to constriction following injury (15 + 1 vs -6 + 3 and 26 + 1 vs -12 + 5% for 10-6M before and after injury respectively). Dynorphin induced dilation was associated with a large increase in CSF cGMP which was blunted following injury. Dilation in response to synthetic selective m, d, and k opioid receptor agonists was similarly altered by brain injury. These data show that opioid induced vasodilation and cGMP production are attenuated following brain injury. Further, these data suggest that altered opioid cerebrovascular effects contribute to pial vasoconstriction following brain injury. 

Received 20 January 1995; accepted in final form 31 May 1995.
APS Manuscript Number H56-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  6 July 1995.