A Study of the Effectiveness of the Iron-Chelating Agent Deferoxamine as Vasospasm Prophylaxis in a Rabbit Model of Subarachnoid Hemorrhage

Abstract

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. SAH resulted in a decrease in basilar artery diameter by 20% on Day 2 and 27% on Day 3. Deferoxamine treatment attenuated the SAH-induced spasm minimally on Day 2 but significantly on Day 3 (Day 3 diameter = 0.60 ± 0.04; P < 0.015). These preliminary results show promise for deferoxamine therapy in the treatment of vasospasm occurring after SAH. These data support the notion that SAH-induced vasospasm is mediated by iron, possibly via the generation of free radicals.