This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Shah, P. K. Search for Related Content PubMed PubMed Citation Articles by Shah, P. K. Related Collections Cardiovascular Pharmacology Pulmonary biology and circulation CV surgery: aortic and vascular disease

(Circulation. 1999;100:333-334.)
© 1999 American Heart Association, Inc.

Editorials

Targeting the Proteolytic Arsenal of Neutrophils

A Promising Approach for Postpump Syndrome and ARDS

Prediman K. Shah, MD

From the Division of Cardiology and Atherosclerosis Research Center, Burns and Allen Research Institute and the Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Dr P.K. Shah, Room 5347, Cardiology Division, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail shahp@cshs.org

Key Words: Editorials • lung • metalloproteinases • cardiopulmonary bypass

	Introduction

 
Of patients who undergo cardiopulmonary bypass (CPB), a procedure essential to most cardiac operations, 1% to 2% develop a syndrome of pulmonary dysfunction called the postpump syndrome, which is analogous to the adult respiratory distress syndrome (ARDS) that develops as a complication of trauma, sepsis, inhalation injury, aspiration pneumonia, pancreatitis, and other disease states.^{1 2} This syndrome is characterized by evidence of pulmonary microvascular endothelial damage, increased microvascular permeability, increased lung water accumulation, increased intrapulmonary shunting, hypoxia, respiratory failure, and a variable severity of clinical expression. Despite many technical and therapeutic advances, the overall mortality associated with this syndrome continues to be high, ranging from 40% to 60%.^{1 2} The precise mechanisms responsible for microvascular damage and tissue destruction in postpump syndrome and ARDS are incompletely understood. An important role for inflammatory cells, specifically neutrophil sequestration and activation, is suggested by a number of experimental and clinical observations.^{3 4 5 6 7} It has been suggested that CPB primes the neutrophils, causing their sequestration in the pulmonary microvasculature, with subsequent activation resulting in the release of tissue-destructive mediators. Several cytokines, such as interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-, and leukemia inhibitory factor, have been implicated in neutrophil recruitment or activation in ARDS.^{6 8 9 10 11 12 13 14} Among various mediators of tissue injury released by activated neutrophils, serine proteases such as elastase and matrix-degrading metalloproteinases have been considered to be most relevant in ARDS.^{3 4 5 6 7 15 16} Experimental observations suggest that neutrophil elastase may serve as an activator of gelatinase B (matrix metalloproteinase [MMP]-9).¹⁷ Both elastase and metalloproteinases, when activated, can induce breakdown . . . [Full Text of this Article]

This article has been cited by other articles:

				E. R. Jacobs and D. C. Zeldin The lung HETEs (and EETs) up Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H1 - H10. [Abstract] [Full Text] [PDF]