Invited commentary

Abstract

This study poses an interesting question: Can the mature lung residual after pneumonectomy be induced to “grow” in a way that yields more functional lung parenchyma? The authors assess the efficacy of retinoic acid (RA), a Vitamin A metabolite, to stimulate parenchymal regeneration after pneumonectomy in a rodent model. In this model, the residual lung hypertrophies during the first 3 weeks after left pneumonectomy, yielding a 60% increase in weight of the right lung. Here the authors demonstrate a striking, rapid increase in lung size, weight, and respiratory airspace volume in animals receiving RA compared to sham thoracotomy animals. Pneumonectomized animals exhibit intermediate increases in lung volumes, and in expression of epidermal growth factor receptor protein. The RA effect is similar to what they have seen previously in this model using epidermal growth factor. The result would be much more interesting if accomplished in more mature animals, or more importantly in an animal model where mesenchymal growth does not continue for the lifetime of the animal. Young adult rats are still in a fairly steep growth phase, and lung growth in this system would not be expected to faithfully model any biologically important phenomenon relevant to adult humans. Further, since rats grow continuously throughout their life span, the possible clinical relevance of any model using this species (or standard farm pigs, which behave similarly) is questionable. These issues impose severe constraints on the value of this model, and on the potential for clinical application of the authors’ findings. It is also of concern that RA treatment tended to be associated with persistent inhibition of weight gain, raising toxicity issues. Nevertheless, proliferation of type II pneumocytes in the setting of a return of alveolar surface density to normal suggests that RA triggered an impressive acceleration in compensatory lung parenchymal growth. A pharmacologic approach to enhance lung growth after resection is biologically interesting. If this “new” lung represents functional tissue, as perhaps measured by diffusing capacity, and if this phenomenon can be duplicated in mature animals, this observation could become clinically important. Retinoic acid enhances lung growth after pneumonectomyThe Annals of Thoracic SurgeryVol. 71Issue 5PreviewBackground. We sought to identify the role of retinoic acid (RA) upon lung growth. RA has a role in perinatal lung development, and we hypothesized that exogenous RA would enhance postpneumonectomy compensatory lung growth.Methods. Utilizing the postpneumonectomy rat model, we studied the impact of RA upon contralateral lung growth. Adult Sprague-Dawley rats were divided into three groups. Group S underwent a sham left thoracotomy, group P underwent left pneumonectomy, and group R underwent left pneumonectomy with administration of exogenous RA (0.5 μg/g/day intraperitoneally). Full-Text PDF