HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article 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 Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): David J. Pinsky Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pinsky, D. J. Articles by Naka, Y. Search for Related Content PubMed Articles by Pinsky, D. J. Articles by Naka, Y.

Ann Thorac Surg 2000;69:891-892
© 2000 The Society of Thoracic Surgeons

---

Commentary

^a Department of Medicine, College of Physicians and Surgeons, Columbia University, PH-10 Stem, 630 W 168th St, New York, NY 10032 USA,

e-mail: djp{at}columbia.edu

Invited commentary

The current science of lung preservation is more of an "art" than a "science." Despite optimal care at harvest and meticulous surgical technique, lung grafts fail in as many as 15% of cases [1] for reasons that are often veiled. New strategies to improve on lung preservation would be a welcome addition in our battle to treat end-stage pulmonary disease with lung transplants, with the hope that improved preservation would translate into reduced morbidity and mortality for the lung graft recipient. Lung preservation practice patterns vary across the nation [2], but in general, "optimal" lung preservation solutions are primarily modified electrolyte solutions. In the current work, Bando and associates use an isolated rat lung perfusion model to study the preservative effects of two ingredients that preserve endothelial homeostasis in the lung graft, a nitric oxide donor (nitroglycerin) and a membrane-permeable cyclic AMP analog (dibutyryl cAMP). These specific ingredients have been previously shown to preserve vascular homeostasis by their ability to promote vasodilation, prevent leukosequestration, inhibit platelet-driven graft thrombosis, and maintain endothelial barrier properties [3, 4]. In the work by Bando and associates, these agents were shown to improve oxygenation and vascular resistance in the ex vivo pulmonary circuit, confirming previous in vivo studies in the lung transplant setting. The data by Bando and associates extend previous studies by showing reduction in peak airway pressure by these two "endothelial cell active" agents. These data are not surprising, given that cyclic nucleotides affect both vascular and airway smooth muscle tone. Beneficial effects of these agents to reduce interstitial pulmonary edema may also be contributory.

In the context of improving lung preservation, it is important to recognize several limitations of this particular ex vivo study. Removal of key cellular (such as neutrophils and platelets) and humoral (complement, coagulation, and fibrinolytic) constituents of blood represents an artificial environment not likely to be encountered in clinical lung transplantation. Furthermore, removal of platelets and leukocytes eliminates known effector mechanisms by which nitroglycerin and db-cAMP function to improve organ preservation. Nevertheless, in spite of eliminating these effector mechanisms in the electrolyte/red cell priming of the perfusion circuit, beneficial effects were obtained. These data confirm the recent study in which a lung preservation solution containing identical doses of nitroglycerin and dibutyryl cAMP caused marked improvement in lung preservation in an in vivo model of lung preservation and transplantation, compared with three other clinically relevant preservation solutions [5]. This mounting evidence for improving vascular preservation in stored grafts by supplementing deficient nitric oxide/cGMP/cAMP second messenger pathways argues strongly for the need for clinical testing of this new preservation strategy.

References

1. Christie J.D., Bavaria J.E., Palevsky H.I., et al. Primary lung graft failure following lung transplantation. Chest 1998;114:51-60.[Abstract/Free Full Text]
2. Hopkinson D.N., Bhabra M.S., Hooper T.L. Pulmonary graft preservation. J Heart Lung Transplant 1998;17:525-531.[Medline]
3. Naka Y., Chowdhury N.C., Liao H., et al. Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine. Requirement for graft vascular homeostasis beyond harvest vasodilation. Circ Res 1995;76:900-906.[Abstract/Free Full Text]
4. Naka Y., Roy D.K., Liao H., et al. cAMP-mediated vascular protection in an orthotopic rat lung transplantation model. Insights into the mechanism of action of prostaglandin E1 to improve lung preservation. Circ Res 1996;79:773-783.[Abstract/Free Full Text]
5. Kayano K., Toda K., Naka Y., Okada K., Oz M.C., Pinsky D.J. Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution. J Thorac Cardiovasc Surg 1999;118:135-144.[Abstract/Free Full Text]

This Article 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 Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): David J. Pinsky Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pinsky, D. J. Articles by Naka, Y. Search for Related Content PubMed Articles by Pinsky, D. J. Articles by Naka, Y.