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Since pathophysiology of vasospasm remains unclear there is
no a successful, targeted therapy. The current treatment of vasos-
pasm is targeted toward increasing cerebral blood fl ow through
maintenance of the high volume of circulating blood, increased
perfusion pressure, and decreased blood viscosity using hyperten-
sion, hypervolemia, and hemodilution (triple-H therapy). The
benefi cial effect on clinical outcome of the triple-H therapy, pio-
neered by Neil Kassell (
24
), has been however questioned (
25
), as
it has been reported that its benefi ts are outweighed by complica-
tions evoked especially by hypervolemia (
25
). This observation led
to the development of 2H-therapy (a name which refl ects a practi-
cal change) that is limited to hypertension and hemodilution.
2H-therapy is gaining popularity all over the world (
26
), especially
as hypervolemia did not show a clear advantage over maintenance
of normovolemia (
25
).
For the last 30 years, the main stream of “preventive” treat-
ment of vasospasm has been a calcium channel blocker nimodipine
(
27
). However, its effectiveness in preventing vasospasm, estab-
lished in the eighties in poorly designed, underpowered clinical
studies, and quite likely biased due to manufacturer sponsorship
(
28, 29
), has been questioned (
30
) and more recently rejected
(
25
). Nevertheless, meta-analysis of nimodipine use in patients
after aSAH has shown that it improves outcomes and reduces cere-
bral infarctions (
27
). Despite this and mostly due to the lack of
preventive effect against vasospasm and its hypotensive effect,
nimodipine administration after aSAH loses support as has been
revealed in the Clazosentan study in which only about 9% of
patients were treated with this calcium channel blocker (
14
).
Long years of failure to establish pathophysiology of vasospasm
and develop preventive treatments have led to the development of
numerous in vitro and in vivo models as well as numerous promising
at fi rst by dissipating quickly, “shooting star” clinical trials. These
failures have allowed us to further our understanding of the vascular
physiology and the regulation of cerebral blood fl ow, as well as rec-
ognize dramatic limitations of the tools we have developed in the
face of the clinical reality of this disease (Fig.
1
; Table
1
).
The challenging enigma of vasospasm and associated clinical
deterioration, despite generally successful treatments of ruptured
aneurysms, have lured hundreds if not thousands of neurosurgeons
and researchers toward seeking its cause, pathomechanism(s), and
developing treatment. Nevertheless, despite this worldwide effort,
developed numerous in vitro and in vivo models, and numbers of
pathophysiological hypotheses tested, the elusive nature of vasos-
pasm pathophysiology remains unrevealed. Over the years, we have
obviously learned a lot about vessels anatomy, physiology, regula-
tion of cerebral blood fl ow, etc., but it seems that as we get closer
to answers we also face the old questions.
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