Pulmonary emphysema is a chronic obstructive lung disease accompanied by debilitation and often resulting in serious pulmonary hypertension and right-heart failure. Development of emphysema appears to be associated with altered connective tissue structure including loss of elastic fibers and disruption of the connective tissue framework. While initiation of the disease is thought to be the result of a destructive event, the progressive nature of the lesion is less well understood. Many investigators believe that it is due to continued activity of degradative enzymes within the lung parenchyma. It is the intent of the studies proposed here to determine if continued breakdown of components of lung connective tissue correlates with progression of the lesion, and if age is associated with increased susceptibility to the progessive phase of the response. In rodents, lungs retain the ability to regenerate tissue with apparently normal architecture. This ability has been reported to vary with age. Following an insult which damages the structure of the lung, however, attempts at repair are ineffective and result in abnormal appearance of the structural framework in the parenchyma. In the studies outlined in this proposal, an animal model of rapid lung growth will be used to extensively radiolabel elastin and collagen. Elastase-induced emphysema will be initited and the rate of loss of radiolabel will be measured and used as an index of degradation of the two proteins. The half-lives of elastin and collagen from control and emphysematous lungs will be calculated and compared directly. Also, by observing the rate of dilution of the specific radioactivity in elastin and collagen, an estimate may be made of the role of """"""""resynthesis"""""""" of these components in response to the lesion. The result of this study will aid in understanding the role of age in respnse to lung injury and in determining the efficacy of current attempts to control emphysema that are based on development of inhibitors of elastase activity in the lung.
