Circulation. 1999;100:e135
(Circulation. 1999;100:e135.)
© 1999 American Heart Association, Inc.
Circulation Electronic Pages |
Pulmonary Clearance of Endothelin-1 on Heart Failure: Reduced or Normal?
Darrel P. Francis
British Heart Foundation Research Fellow
L. Ceri Davies
Robert Luff Foundation Research Fellow
Andrew J. S. Coats
Professor of Cardiology Heart Failure Research
Unit,
Royal Brompton Hospital,
London, UK
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Introduction
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For constant blood flow, percentage extraction is proportional
to
1/endothelin concentration. When a power-law curve is applied
to the
data presented, the best-fit equation spontaneously returns
a
power of -1.02, which directly supports the null hypothesis
(Figure
).
Furthermore, the null
hypothesis, of constant absolute extraction
rate, shows a significant
fit (
R2=0.67) and therefore cannot
be
rejected.
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Figure 1. Application of power-law curve to relationship between plasma
endothelin and percentage pulmonary endothelin
extraction.
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We suggest that the conclusion we should draw from this
innovative study on an important topic is opposite to that implied in
the article. Surely it shows that in heart failure, the increase in
plasma ET-1 occurs despite a constant absolute pulmonary
extraction rate; other candidate causes must therefore be examined.
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References
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-
Dupuis J, Rouleau J-L, Cernacek P. Reduced
pulmonary clearance of endothelin-1 contributes to the increase
of circulating levels in heart failure secondary to myocardial
infarction. Circulation. 1998;98:1684–1687.[Abstract/Free Full Text]
Response
Jocelyn Dupuis, MD, PhD, FRCP;
Jean-Lucien Rouleau, MD;
Peter Cernacek, MD
Department of Medicine,
Montreal Heart Institute,
Montreal, Quebec, Canada
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Introduction
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Francis et al argue that absolute removal of endothelin-1 (ET-1)
by the
lungs would be constant, thus invalidating our main conclusion.
Their
analysis is based on Figure 2 of the article,
1
with assumption
that the in vivo pulmonary flow rate is also
constant. This
second premise is, however, incorrect: although ET-1
extraction
was measured in isolated lungs perfused at a constant flow
rate,
plasma ET-1 levels were measured in vivo, in animals with heart
failure
and presumably variable pulmonary flow rates. To
precisely quantify
absolute pulmonary ET-1 removal would
necessitate the simultaneous
in vivo measurements of
percent ET-1 extraction, pulmonary plasma
flow, and plasma
ET-1 levels.
Following the reasoning of Francis et al, however, one can easily
compute absolute pulmonary ET-1 removal in the isolated lung
studies, since perfusion rate was kept constant with the same amount of
125I-ET-1 injected for each lung. In this
instance, percentage extraction becomes directly proportional to
absolute pulmonary ET-1 removal, thus invalidating the
hypothesis of Francis et al. We have thus clearly demonstrated that
isolated lungs from heart failure rats have a reduced
metabolic capacity to clear ET-1 from circulation and that
this correlates inversely with in vivo ET-1 levels. This, together with
the presence of an increase in arteriovenous ET-1 gradient across the
lungs, suggests that the process contributes to the increase in
circulating levels observed in this model of heart failure.
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References
|
|---|
-
Dupuis J, Rouleau J-L, Cernacek P. Reduced
pulmonary clearance of endothelin-1 contributes to the increase
of circulating levels in heart failure secondary to myocardial
infarction. Circulation. 1998;98:1684–1687.
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Introduction
References