Clinical Scientific Session

The Influens of
Beta Blocker to
Cerebral Infark
at Ischemic
Stroke

By
Rinavi Adrin


dr. Roezwir Azhary, Sp.S

INTRODUCTION
Stroke is a sudden loss of neurologic function
resulting from focal disturbance of cerebral
blood flow due to ischemia or hemorrhage.

Depending on the duration of the
cerebrovascular disturbance, stroke can
cause permanent neurologic damage,
disability, or death
Beta-adrenergic blockers ( beta blockers)
are an important class of drugs for the
treatment of various heart diseases,
including high blood pressure, insufficiency
of blood flow to the heart muscle (angina
pectoris), irregular heart beat (arrhythmias),
thickened heart muscle (hypertrophic
cardiomyopathy), and decreased ability of
the heart to empty or fill normally (heart
failure).
ISCHEMIC STROKE

Stroke is a sudden loss of neurologic function
resulting from focal disturbance of cerebral
blood flow due to ischemia or hemorrhage.

Ischemic stroke is lack of sufficient blood
flow to perfuse cerebral tissue
The mechanisms of ischemia can
generally be divided into 5 main
categories:

thrombosis
embolism
systemic hypoperfusion
arterial luminal obliteration
venous congestion

BETA BLOCKER

Beta-adrenergic blockers ( beta blockers)
are an important class of drugs for the
treatment of various heart diseases,
including high blood pressure, insufficiency
of blood flow to the heart muscle (angina
pectoris), irregular heart beat (arrhythmias),
thickened heart muscle (hypertrophic
cardiomyopathy), and decreased ability of
the heart to empty or fill normally (heart
failure).
BETA BLOCKERS IN ACUTE
ISCHEMIC STROKE
Acute stroke can increase sympathetic activity, a
complication associated with poor outcome.
Based on researched by Karen L. Furie, 2007.

Beta-blockers inhibit the sympathetic response and
have been reported to reduce infarct volume in
animal models.

In Central and peripheral nervous system, blockade
of beta-receptors in the brainstem and of
prejunctional beta-receptors in the periphery inhibits
the release of neurotransmitters and decreases
sympathetic nervous system activity.

In journal Postischemic Brain Injury Is
Attenuated in Mice Lacking the 2
Adrenergic Receptor by Ru-Quan Han, MD
et al explain that Several adrenergic
receptor (AR) antagonists have been
shown to have neuroprotective effects
against cerebral ischemia.
Brain injury is reduced and neurological
outcome improved after MCAO in mice
lacking the 2AR, or in wild type mice
pretreated with a selective 2AR antagonist.
This is consistent with a shift away from
prosurvival signaling to prodeath signaling in
the presence of 2AR activation in cerebral
ischemia.
Protection is associated with higher levels of
Hsp72, a known antideath protein

Based on reseached by Yue TL et al, Carvedilol, a
new antihypertensive drug with unique antioxidant
activity: potential role in cerebroprotection

The data discussed in this article suggest that
carvedilol may not only provide effective and safe
antihypertensive therapy and therefore reduce a
major risk factor for stroke, but will also be better
able to provide additional benefits to patients by
protecting against oxygen free radicals generated
during cerebral ischemia and stroke.
Carvedilol, a widely used antihypertensive agent,
has also been shown to inhibit lipid peroxidation and
to scavenge free radicals in experimental animals.

Free radicals lead to excitotoxicity and are
neurotoxic to the ischemic brain areas either
following or enhancing glutamate release.

Carvedilol has been shown to inhibit the release of
human neutrophil-generated superoxide and
superoxide radicals
In vitro, primary cultures of rat cerebellar neurons
with free radical generating system were used.
Carvedilol inhibits the DHF-Fe+3/ADP free radical-
generating system and Fe+2/vitamin C-catalyzed
lipid peroxidation.

In vivo, CA1 hippocampal neurons were
protected against oxygen free radicals,
suggesting carvedilol's potential as a therapeutic
agent in ischemic stroke
In journal The novel beta-blocker, carvedilol,
provides neuroprotection in transient
focal stroke by Savitz SI et al,

Carvedilol is a mixed adrenergic antagonist,
and that it behaves as an antioxidant and
inhibits apoptosis.
In the current study, the authors investigated
whether carvedilol provides protection in focal
cerebral ischemia and whether this protection is
associated with reduced apoptosis and the
downregulation of the inflammatory cytokines,
tumor necrosis factor-alpha (TNF-alpha) and
interleukin- 1beta (IL-1beta)
The results of the current study indicate that
carvedilol is neuroprotective in focal
cerebral ischemia and may protect
the ischemic brain by inhibiting apoptosis and
attenuating the expression of TNF-alpha and IL-
1beta.

REFERENCES

1. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics2008
update: a report from the American Heart Association Statistics Committee and
Stroke Statistics Subcommittee. Circulation 2008;117:e251
2. The novel beta-blocker, carvedilol, provides neuroprotection in transient
focal stroke.Savitz SI, Erhardt JA, Anthony JV, Gupta G, Li X, Barone
FC, Rosenbaum DM.
3. Carvedilol, a new antihypertensive drug with unique antioxidant activity:
potential role in cerebroprotection..Yue TL, Lysko PG, Barone FC, Gu JL, Ruffolo RR
Jr, Feuerstein GZ.
4. Ischemic Stroke: Pathophysiology and Principles of Localization, 2009
5. Expert consensus document on b-adrenergic receptor blockers, 2004, europan
heart journal
6.Alkayed NJ, Goyagi T, Joh HD, et al. Neuroprotection and P450 2C11
upregulation after experimental transient ischemic attack. Stroke 2002;33:1677
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