Effect of Deferoxamine and Sympathectomy on Vasospasm following Subarachnoid Hemorrhage

Abstract

We examined the effects of subarachnoid hemorrhage (SAH) and treatment with deferoxamine (DFO) or sympathectomy on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording the responses to nor-adrenaline and serotonin in isolated carotid arteries in vitro. All studies were performed before and 7 days after SAH. An experimental subarachnoid hemorrhage model was created in rabbits by injecting autologous arterial blood into the subarachnoid space of the rabbits via cisterna magna punction. During the chronic stage of vasospasm following SAH deferoxamine (DFO) was given to the animals and cervical and periarterial sympathectomy was performed in the other groups of animals. In isolated carotid arteries noradrenaline (10^–8 to 10^–4 mol/l) and serotonin (10^–8 to 10^–4 mol/l) produced concentration-dependent contractions. These contractile responses were significantly enhanced in animals 7 days after SAH compared to controls and did not return to control values in carotid arteries obtained from animals treated with DFO or sympathectomy for 7 days after SAH. These results show that SAH causes supersensitivity in the carotid as well as cerebral arteries during the first week after SAH and could contribute to the development of cerebral vasospasm. Both treatment with DFO and sympathectomy after SAH did not reduce the contractile responses to noradrenaline and serotonin in the carotid arteries. In conclusion, treatment with DFO or sympathectomy during the chronic stage of vasospasm after SAH did not affect the vascular responses of the extradural part of the carotid artery to vasoactive substances.

Heme oxygenase-1-mediated neuroprotection in subarachnoid hemorrhage via intracerebroventricular deferoxamine

“…A potential explanation is that ICV administration allows for proximity to the heme burden, while IP-administered DFX has to effectively cross the blood brain barrier. Second, DFX provided cerebral protection and improved cognition after SAH independent of any effect on vasospasm, similar to previous studies that showed DFX treatment had no effect on vascular response after SAH [ 47 , 48 ]. Vasospasm-independent cerebral protection provided by DFX is not surprising when one considers recent clinical trials that effectively treated vasospasm but did not improve morbidity or mortality after SAH [ 7 , 8 ].…”

Elucidating the progress and impact of ferroptosis in hemorrhagic stroke

“…In 1988, the non-glucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, alleviated the acutely progressive hypoperfusion state in a cat SAH model ( Hall and Travis, 1988 ). In the early 1990s, Utkan et al (1996) demonstrated for the first time that the iron chelator DFO could prevent SAH-induced vasospasm in a rabbit model ( Utkan et al, 1996 ). They also hypothesized that the underlying mechanism might involve the inhibition of iron-induced ROS and lipid peroxides ( Utkan et al, 1996 ).…”

“…In the early 1990s, Utkan et al (1996) demonstrated for the first time that the iron chelator DFO could prevent SAH-induced vasospasm in a rabbit model ( Utkan et al, 1996 ). They also hypothesized that the underlying mechanism might involve the inhibition of iron-induced ROS and lipid peroxides ( Utkan et al, 1996 ). Subsequent studies have repeatedly demonstrated the reduction of vasospasm by iron chelation ( Luo et al, 1995 ).…”