Ann Thorac Surg 2006;82:471
© 2006 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Invited commentary
Ashish S. Shah, MD,
John V. Conte, MD
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Blalock 618, 600 N Wolfe St, Baltimore, MD 21287
(Email: ashah{at}duke.edu; jconte{at}csurg.jhmi.jhu.edu).
Donor organ manipulation on the molecular level has been an intriguing, exciting, and elusive proposition. As we learn more about donor organ function and dysfunction, it is clear that modulating receptors systems and inflammatory mediators may allow for improved allograft function. A variety of approaches are available, including gene transfer strategies, transgenic technology, and pharmacologic interventions. Nonetheless, very little from this fertile area of research has found its way into clinical lung transplantation to date.
Chen and colleagues [1] have presented a simple experiment to examine the effects of inhaled ß2 agonist on lungs subjected to warm ischemia. Using an isolated rat lung perfusion model, the authors subjected lungs to warm ischemia and controlled reperfusion with and without inhaled salmeterol. They looked at pulmonary function, weight, and vascular resistance, as well as cyclic AMP (cAMP), energy substrates, and myeloperoxidase activity. They report that warm ischemia causes acute reduction in cAMP levels, that short-term inhalation of salmeterol prevents this reduction and in turn leads to better lung function after reperfusion.
The study is limited in a variety of ways. There is no mention of changes in oxygenation and basic gas exchange throughout the experiment. No histology is presented. It is also a short experiment, and whether the initial improvement in pulmonary function is stable is untested. Different species have variable responses to ischemia and ß-adrenergic stimulation in the lung so it will be difficult to extrapolate these results. Furthermore, polymorphisms and desensitization in human ß-receptors have significant effects on responses to agonists so the clinical utility of salmeterol may be inconsistent. Finally, the authors have certainly shown an association between increased cAMP and improved acute tolerance of warm ischemia, but causation is a more difficult conclusion. Cyclic AMP is a common second messenger with a variety of downstream effects in the lungs. Future studies will be needed to further explore where the protective effect in this model resides (ie, kinases, sodium transporters, and so forth).
Nonetheless, Chen and colleagues [1] have examined a simple and clinically relevant intervention that may be applicable to cadaveric as well as nonheart beating donors. More work on improving and expanding the donor lung pool is desperately needed, and this area of research remains clinically important.
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References
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- Chen F, Nakamura T, Fujinaga T, et al. Protective effect of a nebulized ß2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs Ann Thorac Surg 2006;82:465-471.[Abstract/Free Full Text]
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