This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Francis, D. P. Articles by Cernacek, P. Search for Related Content PubMed PubMed Citation Articles by Francis, D. P. Articles by Cernacek, P.

(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

	Introduction

 
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.

View larger version (23K): [in this window] [in a new window]   Figure 1. Application of power-law curve to relationship between plasma endothelin and percentage pulmonary endothelin extraction.

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.

	References

 
1. 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

	Introduction

 
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 . . . [Full Text of this Article]