title: Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postischemic hypoperfusion.
abstract: Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.
authors.affiliation: Neurosurgery Service, Massachusetts General Hospital, Boston 02114.
authors.forename: R
authors.initials: R
authors.lastname: Macfarlane
authors.forename: E
authors.initials: E
authors.lastname: Tasdemiroglu
authors.forename: M A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: Y
authors.initials: Y
authors.lastname: Uemura
authors.forename: E P
authors.initials: EP
authors.lastname: Wei
authors.forename: H A
authors.initials: HA
authors.lastname: Kontos
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015171:Ganglionectomy; D006940:Hyperemia / Q000503:physiopathology* / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D010841:Pia Mater / Q000098:blood supply*; D013373:Substance P / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000502:physiology* / Q000601:surgery; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin