A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage.
The pathogenesis of cerebral vasospasm occurring after subarachnoid hemorrhage (SAH) is unknown. Several lines of experimentation have suggested a free radical mechanism in the etiology of vasospasm. Iron is an important catalyst in the generation of free radicals and lipid peroxides in response to tissue injury. We hypothesize that the elaboration of iron from the subarachnoid clot might result in enhanced generation of free radicals and lipid peroxidation. If so, then treatment with deferoxamine, an iron-chelating compound, might reduce the formation of free radicals and thereby ameliorate vasospasm. This hypothesis was examined in a rabbit model of experimental cerebral vasospasm. New Zealand White rabbits were divided into the following experimental groups: control (normal) animals (n = 7), control animals treated with deferoxamine (n = 3), animals subjected to SAH and killed on Day 2 (n = 7), animals subjected to SAH on Day 2 and treated with deferoxamine (n = 9), animals subjected to SAH killed on Day 3 (n = 7), and animals subjected to SAH on Day 3 and treated with deferoxamine (n = 7). Deferoxamine treatment (50 mg/kg/8 hours) was begun 16 hours before the induction of SAH and continued until the animals were killed by perfusion fixation. The basilar artery caliber was assessed using morphometric techniques. The diameter of the basilar arteries in the control animals was 0.64 +/- 0.02 mm. Deferoxamine treatment alone did not alter the artery diameter.(ABSTRACT TRUNCATED AT 250 WORDS)
Vollmer
D G
DG
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri.
Hongo
K
K
Ogawa
H
H
Tsukahara
T
T
Kassell
N F
NF
D000818:Animals; D001488:Basilar Artery / Q000473:pathology; D001921:Brain / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000503:physiopathology
D007502:Iron Chelating Agents; D003676:Deferoxamine