The effect of subarachnoid hemorrhage (SAH) on endotbelium-dependent vasodilation of isolated rabbit basilar artery was examined using an isometric tension recording method. Thirty-five rabbits that had 2 successive blood injections were divided into 3 groups: normal animals (control), 4 days, and 3 weeks after the first SAH. Acetylcholine (ACh) (10~6-10~4 M) and adenosine triphosphate (ATP) (10~6-10~4 M) were used to evoke dose-dependent vasodilation of isolated arterial rings previously contracted by 10~6 M serotonin. In the animals killed 4 days after the first SAH, both AChand ATP-induced relaxation were suppressed, and the degree of relaxation of this group was 38 ± 4.5% (mean ± SEM) and 22 ± 3.9% of the initial contractile tone in response to 10" 3 Despite extensive efforts to identify measures to dilate the narrowed arteries, no reliable measure exists for preventing vasospasm from developing or for reversing it. One of the major reasons for this inadequacy is a lack in understanding the pathogenesis of vasospasm. The cause of cerebral vasospasm following SAH is likely to be multifactorial.It has been recently suggested that impairment of the vasodilatory activity of cerebral arteries following SAH may play an important role in the pathogenesis of vasospasm. Arterial wall prostacyclin, a powerful vasodilator, decreases progressively following SAH. 8 It is well documented that endothelial damage occurs frequently after SAH. We have recently demonstrated that endothelium-dependent vasodilation induced by adenosine triphosphate (ATP) is impaired after SAH in a rabbit single hemorrhage model (T. Nakagomi, unpublished data). However, acetylcholine (ACh)-induced vasodilation was well preserved following SAH in that model. This may reflect a partial, less severe damage to the endothelium. The present experiments were conducted to investigate 1) the effect of SAH on endothelium-dependent vasodilation induced by ACh and ATP in a rabbit double hemorrhage model, which should result in more severe damage to the endothelium than a single injection model, and 2) to study the inhibitory effect of hemoglobin on endothelium-dependent vasodilation in basilar arteries exposed to SAH.
Materials and Methods
Animal PreparationsThirty-five male New Zealand white rabbits weighing 2.9-3.4 kg were anesthetized with an i.m. injection of ketamine (20 mg/kg), xylazine (5 mg/kg), and acepromazine (0.25 mg/kg) in a ratio of 8:1:1. The animals were intubated and received muscular paralysis with i.v. pancuronium bromide (0.08 mg/kg). Ventilation was maintained with a Harvard dual-phase control respirator. In each animal, the left ear artery was cannulated for monitoring blood pressure and withdrawing arterial blood.A 23-gauge butterfly needle was inserted into the cisterna magna percutaneously and connected to a pressure transducer via one outlet of a three-way stopcock. The other outlet was used for the injection of arterial blood. Intracranial pressure (ICP) was monitored immediately after the injection of arterial blood through the st...