title: Rectal temperature and prostaglandin E2 increase in cerebrospinal fluid of conscious rabbits after intracerebroventricular injection of hemoglobin.
abstract: Fever accompanies subarachnoid hemorrhage (SAH) in the majority of patients. In a previous study, hemoglobin (Hb) was shown to catalyze in vitro, under aerobic conditions, the conversion of arachidonic acid to prostaglandin E2 (PGE2) and prostaglandin F2alpha. The aim of the present work was to assess whether this pathway also operates in vivo and to provide a mechanism to explain post-SAH fever. To this end, PGE2 concentration was determined in cerebrospinal fluid (CSF) of conscious rabbits chronically cannulated in the lateral ventricle and cisterna magna, following intracerebroventricular (i.c.v.) injection of 10 microg or 100 microg of commercial rabbit bicrystallized Hb as a model of SAH. Before i.c.v. injection, Hb solutions were filtered on a polimixin-B column to remove substantially, by over 90%, endotoxin-like substances. Results show that in nine rabbits injection of 10 microg Hb did not significantly modify body temperature or significantly alter CSF PGE2 content. On the contrary, in nine rabbits, injection of 100 microg Hb produced a significant increase in core temperature which was accompanied by a significant increase in CSF PGE2. When data related to these two parameters from the 9 control and 18 Hb-treated rabbits were analyzed as a single group, a linear, positive, and highly significant correlation was found. These findings indicate that, once Hb is released into the subarachnoid space during SAH, it enhances CSF PGE2 content and elicits hyperthermia, thus offering an explanation for the fever that is an aggravating condition in most SAH patients.
authors.affiliation: Istituto di Scienze Farmacologiche, University of Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Frosini
authors.forename: C
authors.initials: C
authors.lastname: Sesti
authors.forename: M
authors.initials: M
authors.lastname: Valoti
authors.forename: M
authors.initials: M
authors.lastname: Palmi
authors.forename: F
authors.initials: F
authors.lastname: Fusi
authors.forename: L
authors.initials: L
authors.lastname: Parente
authors.forename: G
authors.initials: G
authors.lastname: Sgaragli
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000502:physiology*; D003243:Consciousness; D015232:Dinoprostone / Q000134:cerebrospinal fluid*; D004573:Electrolytes / Q000134:cerebrospinal fluid; D004926:Escherichia coli; D005334:Fever / Q000503:physiopathology; D006454:Hemoglobins / Q000008:administration & dosage / Q000502:physiology*; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D012044:Regression Analysis; D013345:Subarachnoid Hemorrhage
chemical_list: D004573:Electrolytes; D006454:Hemoglobins; D008070:Lipopolysaccharides; D015232:Dinoprostone