Attenuation of cerebral vasospasm in rabbits using clonidine hydrochloride, a central adrenergic agonist.
The aim of this study was to assess, firstly, if exclusion of central noradrenergic areas in the hypothalamus and brain stem with the central sympathetic blocker clonidine hydrochloride could prevent the development of chronic vasospasm following experimental subarachnoid haemorrhage in rabbits and, secondly, if, parallel with the effect on cerebral arteries, changes in dopamine beta-hydroxylase concentration in the hypothalamus and brain stem could also be detected. Experimental subarachnoid haemorrhage, in concentrations of 1 ml of autologous arterial blood/1 kg of body weight was carried out on 18 New Zealand rabbits. Histological specimens were obtained by the method of perfusion fixation after the rabbits were sacrificed on day 8 after subarachnoid haemorrhage. The spastic effect of experimentally induced subarachnoid haemorrhage was determined by assessing the intensity of corrugation of the intima of the rabbit basilar artery by the previously developed method of corrugation coefficient and computer image analysis. The concentration and localization of dopamine beta-hydroxylase in noradrenaline-containing neurons was immunohistochemically assessed (semiquantitatively as 0, 1 and 2) with anti-dopamine beta-hydroxylase, at precisely defined sites of the hypothalamus and brain stem of the same rabbit. The results revealed less corrugated and smoother intima in the basilar artery and significantly lower dopamine beta-hydroxylase concentration in the control group of rabbits with sham subarachnoid haemorrhage and without any additional interventions (mean corrugation coefficient=1.123+/-0.024, P=0.35 x 10(-3); mean dopamine beta-hydroxylase=0.350+/-0.071, P=0.22 x 10(-3)), and smoother intima in the basilar artery with significantly lower concentration of dopamine beta-hydroxylase in the clonidine group (rabbits with subarachnoid haemorrhage and central alpha(2)-blocker clonidine hydrochloride at a daily dose of 0.03 mg/kg of body weight for 8 days; mean corrugation coefficient=1.177+/-0.058, P=1.7 x 10(-3); mean dopamine beta-hydroxylase=0.583+/-0.175, P=1.1 x 10(-3)). In comparison, the haemorrhage only group (rabbits with subarachnoid haemorrhage and without medication; mean corrugation coefficient=1.370+/-0.101; mean dopamine beta-hydroxylase=1.214+/-0.313) displayed intensive corrugation of the intima of the basilar artery and a significantly more intensive accumulation of dopamine beta-hydroxylase than did the control group and the clonidine group. The results of this study demonstrated that the central alpha(2)-blocker clonidine hydrochloride effectively prevents vasospasm, and diminishes the concentration of cerebral dopamine beta-hydroxylase in the hypothalamus and brain stem after experimental subarachnoid haemorrhage in rabbits.
Department of Neurosurgery, Maribor Teaching Hospital, Ljubljanska 5, Maribor SI-2000, Slovenia. gorazd.bunc@sb-mb.si
Gorazd
G
Bunc
Srecko
S
Kovacic
Simona
S
Strnad
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D003000:Clonidine / Q000627:therapeutic use*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D011817:Rabbits; D020301:Vasospasm, Intracranial / Q000097:blood / Q000188:drug therapy*
D000316:Adrenergic alpha-Agonists; D004299:Dopamine beta-Hydroxylase; D003000:Clonidine