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Success of cardiac glycosides in prevention of ischemic stroke
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keith
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Joined: 07 Apr 2006
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PostPosted: Wed Jul 12, 2006 2:08 pm    Post subject: Success of cardiac glycosides in prevention of ischemic stroke Reply with quote

A breakthrough in stroke prevention. Published at
http://www.i-newswire.com/pr68572.html

Keith

Cardiac glycosides in prevention of ischemic stroke

Brazilian study confirm the findings of Duke University Medical Center
researchers that cardiac glycosides provide neuroprotection in stroke
occurrence. It was a study of 28 years that showed a low mortality for
stroke in 1150 cardiac patients taking these drugs.

ICP (I-newswire) -- Using a novel screening technology, Duke University
Medical Center researchers have shown that drugs called cardiac
glycosides can protect brain cells from death after stroke in
laboratory models, and that the drugs are effective even if delivered
six hours or more after the onset of stroke conditions (1).

"This discovery is exciting because it may lead to interventions to
prevent or lessen the amount of brain damage suffered after stroke,"
said Donald C. Lo, Ph.D., director of the Center for Drug Discovery and
associate professor of neurobiology at Duke, and primary investigator
on the study
Currently, only one drug has been approved by the Food and Drug
Administration to treat stroke -- and it faces serious limitations, Lo
said. Called recombinant tissue plasminogen activator, the drug must be
given within a three-hour window after the onset of stroke. Also,
because the drug is delivered intravenously and acts by breaking blood
clots, it is ineffective against "hemorrhagic" strokes that happen when
an artery bursts.

Lo speculates that cardiac glycosides may exert their beneficial effect
during stroke in an analogous manner that in heart disease, by
restoring calcium to healthy levels in brain cells and thereby
preventing cell death. Calcium plays a key role in regulating normal
cell function, and any changes in its cellular concentration -- such as
those caused by stroke -- can be toxic (2).
Another recent study with statin drugs concluded that its use is
associated with a reduced risk of stroke but not severity or mortality
(3)

Related to the Duke University Medical Center research, a case study
from Brazil confirm the very low mortality for stroke in 1150 patients
with stable heart disease taking cardiac glycosides, during 28 years.
The study was authored by Quintiliano H. de Mesquita and Claudio A. S.
Baptista and published in Ars Cvrandi, a Brazilian medical journal in
2002 (4)

The stroke (ischemic + hemorrhagic) mortality in 28 years for the
cardiac patients taking cardiac glycosides was:

- 994 patients w/out prior infarction - Stroke mortality: 13 cases
(1.3%) = 0.04% per year.
- 156 patients with prior infarction - Stroke mortality: 7 cases (4.4%)
= 0.15% per year.

For a better comparison in stroke mortality, with those taking cardiac
glycosides, we can take the data from the HPS study, which had a
follow-up of 5 years, involving 20.536 patients aged 40-80 years with
coronary heart disease, other vascular diseases or diabetes. The HPS
found a total stroke mortality of 0.9% (0.18% per year) in patients
taking statins and 1.2% (0.24% per year) in patients taking placebo (5)

The permanent use of cardiac glycosides (Digitoxin, Digoxin,
Acetildigoxin, Lanatoside-C, Betametildigoxin, or Proscillaridin-A) in
low, daily therapeutic (non-toxic) doses from the Brazilian study was
based on the Myogenic Theory of Myocardial Infarction and had as its
objective the prevention of acute coronary syndromes (6, 7). The global
mortality for the patients without previous myocardial infarction was
14.2% (0.5% per year), while the global mortality for the patients with
previous myocardial infarction was 41.0% (1.4% per year). The numbers
for mortality and morbidity are described in the Table 5 of the
article. (1)

References

1. Cardiac glycosides provide neuroprotection agains ischemic stroke:
Discovery by a brain slice-based compound screening platform, James K.
T. Wang, Donald C. Lo et al, Proc Natl Acad Sci U S A. 2006 Jun 22;
Full and free text at
http://www.pubmedcentral.gov/picrender.fcgi?artid=1481664&blobtype=pdf
2. Study Spots Potential Stroke Drugs,
http://www.dukemednews.org/news/article.php?id=9754
3. Statin use and sex-specific stroke outcomes in patients with
vascular disease, Cheryl D. Bushnell et al, Stroke, 2006; 37:1427
4. Cardiotonico: Insuperavel na Preservacao da Estabilidade Miocardica
como Preventivo das Sindromes Coronarias Agudas e Responsavel pela
Prolongada Sobrevida--Casuistica de 28 anos (1972-2000), Mesquita, QHde
e Baptista, CAS. Ars Cvrandi. May 2005, Volume 35, republished in 2005
at http://www.infarctcombat.org/28anos/digitalicos.html, with summary
in English at http://www.infarctcombat.org/heartnews-16.html.
5. The effects of cholesterol lowering with simvastatin on
cause-specific mortality and on cancer incidence in 20,536 high-risk
people: a randomized placebo-controlled trial, Heart Protection Study
Collaborative Group. BMC Medicine 2005, 3:6 --
http://www.biomedcentral.com/1741-7015/3/6
6. Myogenic Theory of Myocardial Infarction Book with summary in
English at http://www.infarctcombat.org/LivroTM/parte8.htm.
7. Some articles in English about the Myogenic Theory are available at:
http://www.infarctcombat.org/MyogenicTheory.html.
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