Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pearse, D. B.
Right arrow Articles by Dodd-o, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pearse, D. B.
Right arrow Articles by Dodd-o, J. M.
(Chest. 1999;116:55S-56S.)
© 1999 American College of Chest Physicians

Ischemia-Reperfusion Lung Injury Is Prevented by Apocynin, a Novel Inhibitor of Leukocyte NADPH Oxidase*

David B. Pearse, MD and Jeffrey M. Dodd-o

* From the Johns Hopkins University, Baltimore, MD. Supported by grant HL-50504 from the National Institutes of Health.

Correspondence to: David B. Pearse, MD, Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224

Ischemia and reperfusion (IR) of isolated sheep lungs caused polymorphonuclear leukocyte (PMN) sequestration, pulmonary hypertension secondary to thromboxane (TX), edema, and increased vascular permeability.1 PMN depletion attenuated this injury, suggesting that PMN-derived O2 radicals were involved.2 Apocynin (Apo) is a methoxy-substituted catechol that requires activation by myeloperoxidase to inhibit the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and thus prevents O2- production from activated PMN leukocytes. To determine the effect of Apo in IR injury, we subjected 20 sheep lungs to 30 min of ischemia and 180 min of reperfusion with blood. We injected 3 mM, 0.3 mM, 0.03 mM Apo, or diluent (n = 5 each) into the pulmonary artery early in ischemia and the reservoir before reperfusion. Peak pulmonary artery pressure, peak perfusate TXB2 concentration, and the reflection coefficient for albumin were measured (Table 1) . The ability of Apo to inhibit in vitro O2- production from zymosan-activated sheep PMN leukocytes was also assessed (n = 3).


View this table:
[in this window]
[in a new window]

  		Table 1. Measurements

 
In a dose-dependent manner, Apo prevented the increased vascular permeability, pulmonary hypertension, and TX release associated with IR injury. The correlation of these effects with inhibition of O2- production from PMN leukocytes in vitro suggests that Apo protected by inhibiting leukocyte NADPH oxidase. Apo may represent a new therapeutic approach to the clinical problem of reperfusion lung injury.

References

  1. Pearse, DB, Sylvester, JT (1996) Vascular injury in isolated sheep lungs: role of ischemia, extracorporeal perfusion, and oxygen. Am J Respir Crit Care Med 153,196-202[Abstract]
  2. Pearse, DB, Brower, RG, Adkinson, NF, Jr, et al (1989) Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets. J Appl Physiol 66,1287-1296[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
I. Rubio-Gayosso, S. H. Platts, and B. R. Duling
Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury
Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2247 - H2256.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Takase, L. Lerond, J. J. Bergan, and G. W. Schmid-Schonbein
Enhancement of reperfusion injury by elevation of microvascular pressures
Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1387 - H1394.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pearse, D. B.
Right arrow Articles by Dodd-o, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pearse, D. B.
Right arrow Articles by Dodd-o, J. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS