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 β-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 β-hydroxylase in noradrenaline-containing neurons was immunohistochemically assessed (semiquantitatively as 0, 1 and 2) with anti-dopamine β-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 β-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=0.35×10−3; mean dopamine β-hydroxylase=0.350±0.071, P=0.22×10−3), and smoother intima in the basilar artery with significantly lower concentration of dopamine β-hydroxylase in the clonidine group (rabbits with subarachnoid haemorrhage and central α2-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=1.7×10−3; mean dopamine β-hydroxylase=0.583±0.175, P=1.1×10−3). In comparison, the haemorrhage only group (rabbits with subarachnoid haemorrhage and without medication; mean corrugation COEFFICIENT=1.370±0.101; mean dopamine β-hydroxylase=1.214±0.313) displayed intensive corrugation of the intima of the basilar artery and a significantly more intensive accumulation of dopamine β-hydroxylase than did the control group and the clonidine group. The results of this study demonstrated that the central α2-blocker clonidine hydrochloride effectively prevents vasospasm, and diminishes the concentration of cerebral dopamine β-hydroxylase in the hypothalamus and brain stem after experimental subarachnoid haemorrhage in rabbits.