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  • 1
    Electronic Resource
    Electronic Resource
    Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage (1990)
    Springer
    Acta neurochirurgica 107 (1990), S. 11-15 
    Details
    ISSN: 0942-0940
    Keywords: Subarachnoid haemorrhage ; chronic cerebral vasospasm ; calcium antagonist ; AT877 ; HA 1077
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibiton of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120–180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo-controlled double-blind trial (which is currently being carried out).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01402606
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  • 2
    Electronic Resource
    Electronic Resource
    The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs (1988)
    Springer
    Acta neurochirurgica 90 (1988), S. 53-59 
    Details
    ISSN: 0942-0940
    Keywords: Calcium antagonist ; chronic cerebral vasospasm ; HA 1077 ; subarachnoid haemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nefedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10−6 M HA 1077 for the “intracranial” basilar and middle cerebral arteries, while a 10−5 M was needed to obtain the same effect for the “extracranial” common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the “two haemorrhage” model of Varsoset al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5–3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20–30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time. Such spasmolytic effects by intravenous administration could not have been obtained with the usual calcium channel blockers. HA 1077 may be suitable for the treatment of a vasospasm in humans as well.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01541267
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of prophylactic intrathecal administrations of nicardipine on vasospasm in patients with severe aneurysmal subarachnoid haemorrhage (1994)
    Springer
    Acta neurochirurgica 131 (1994), S. 19-25 
    Details
    ISSN: 0942-0940
    Keywords: Cerebral vasospasm ; cerebral aneurysm ; calcium antagonist ; nicardipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Calcium antagonists are currently most widely used for chronic cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). However, the vasodilatory effects of systemically administered calcium antagonists can be limited secondary to hypotension. We previously compared intrathecal and intravenous routes of administration of nicardipine. Intrathecal administration of nicardipine significantly dilated spastic basilar arteries on day 7 in a two-haemorrhage canine model of vasospasm. In the present communication, the effects of prophylactic, serial administration of intrathecal nicardipine on vasospasm was examined in 50 patients. Patients were classified as Fisher SAH group 3 and all had their aneurysms clipped within 3 days of SAH. Following placement of a cisternal drain, 2 mg of nicardipine was injected, three times each day for an average of 10 days. The control group consisted of 91 similar patients with cisternal drainage not treated with nicardipine. Intrathecal administration of nicardipine decreased the incidence of symptomatic vasospasm by 26%, angiographic vasospasm by 20% and increased good clinical outcome at one month after the haemorrhage by 15%. Postoperative angiograms revealed that patients in the nicardipine group showed less vasospasm of major cerebral arteries, near the tip of a drain in the basal cistern, but vasospasm in the A2 and M2 segments was not decreased. Radio-isotope cisternography suggested that nicardipine might not reach the subarachnoid space around A2 and M2 segments. Nine patients complained of headache probably secondary to nicardipine induced vasodilation. Two patients suffered from mengingitis, both were successfully treated. Intrathecal administration nicardipine appears to be effective in the treatment of vasospasm, but side effects were significant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01401450
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  • 4
    Electronic Resource
    Electronic Resource
    The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs (1991)
    Springer
    Acta neurochirurgica 110 (1991), S. 185-188 
    Details
    ISSN: 0942-0940
    Keywords: HA1077 ; cerebral vasospasm ; subarachnoid haemorrhage ; cerebral blood flow ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p〈0.05) and Hood velocity (48% of control, p〈0.05), with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1–0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01400689
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