Leukotrienes, Prostaglandins, and Granulocyte Accumulation in Cerebral Ischemia
Abstract
Granulocytes accumulate during the early hours of the postischemic period in a canine model of multifocal ischemia induced by air embolism. This accumulation could theoretically aggravate and extend the initial tissue injury through one of several mechanisms. Granulocytes synthesize arachidonic acid metabolities such as prostaglandins, leukotrienes, and hydroxy acids capable of producing local vasoconstriction and increased microvascular permeability. They also produce superoxide and other free radical products, release hydrolytic enzymes from intracellular granules, and synthesize platelet activating factor. It would seem reasonable to predict that modulation of arachidonic acid metabolism would affect the accumulation of granulocytes in ischemic brain, cerebral blood flow in the injury zone, and postischemic recovery of neuronal function as indicated by the cortical somatosensory evoked response (CSER). Specifically, cyclooxygenase inhibition (indomethacin) combined with PGI2 and heparin should augment the CSER and eliminate 'neuron-disabling' blood flows after ischemia as previously observed. Granulocyte accumulation under these conditions should be more pronounced due to the increased formation rate of chemotactic products of the lipoxygenase pathway that accompanies cyclooxygenase inhibition. Substitution of dual cyclooxygenase and lipoxygenase inhibition (BW 755 C) for the indomethacin should reduce the accumulation of granulocytes and, by restriction access of these potentially human cells to the injury zone, foster a relatively greater CSER recovery. These predictions were tested in the canine model of focal ischemia induced by incremental air embolism. Reprints.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1987
- Accession Number
- ADA198623
Entities
People
- A. J. Dutka
- J. M. Hallenbeck
- K. K. Kumaroo
- P. M. Kochanek
- T. Tanishima
Organizations
- Naval Medical Research Center