title: Low-dose prostacyclin improves cortical perfusion following experimental brain injury in the rat.
abstract: It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.
authors.affiliation: Department of Physiological Sciences, University of Lund and Lund University Hospital, Lund, Sweden. peter.bentzer@mphy.lu.se
authors.forename: Peter
authors.initials: P
authors.lastname: Bentzer
authors.forename: Daniele
authors.initials: D
authors.lastname: Venturoli
authors.forename: Ola
authors.initials: O
authors.lastname: Carlsson
authors.forename: P-O
authors.initials: PO
authors.lastname: Grände
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002199:Capillary Permeability; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects* / Q000293:injuries; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000493:pharmacokinetics; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D004492:Edetic Acid; D011464:Epoprostenol