Pulmonary air-space enlargement induced by intratracheal instillment of hyaluronidase and concomitant exposure to 60% oxygen.
Although emphysema is generally characterized by damage to pulmonary elastic fibers, the causes of such injury appear to be complex and are not entirely explained by a singular imbalance between elastases and their inhibitors. Other factors could compromise elastic fiber integrity. To test the validity of this argument, hamsters were instilled intratracheally with a nonelastolytic enzyme, hyaluronidase (which reduces lung hexuronic acid content by 21% after 24 h), then exposed to an otherwise nontoxic concentration of oxygen (60%) for 4 days. Additional groups were given (1) hyaluronidase and room air, (2) saline and 60% oxygen, and (3) saline and room air. Treatment with both hyaluronidase and 60% oxygen resulted in a significant increase in air-space enlargement at 4 days (67.1 vs. 57.9 microns for saline/room air controls; p < .05), which was accompanied by only minimal inflammatory changes, as determined by both light microscopy and lavage cytology. Animals receiving either hyaluronidase or 60% oxygen alone showed no significant increases in air-space size compared to those given saline and exposed to room air. While the mechanisms responsible for these results are unclear, the marked increase in radiolabeling of lung elastin cross-links (desmosine and isodesmosine) in animals receiving both hyaluronidase and 60% oxygen (429 vs. 168 cpm/g dry lung for saline/room air controls; p < .05), as well as a significant decrease in total lung desmosine and isodesmosine (32.5 vs. 37.7 micrograms/lung for saline/room air controls; p < .05), suggests that elastic fiber damage is a potential factor. Moreover, only those animals receiving both hyaluronidase and 60% oxygen showed a significant rise in cell-free elastase activity in lavage fluids compared to saline/room air controls (83.3 vs. 48.3 ng; p < .05). On the basis of these findings, it is concluded that while elastic fiber damage may be a common pathway in emphysema, the factors that initiate the disease may be more varied than previously suspected and not always related to the balance between elastases and their inhibitors.
Cantor
J O
JO
Columbia University College of Physicians and Surgeons, New York, NY.
Cerreta
J M
JM
Armand
G
G
Keller
S
S
Turino
G M
GM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology; D006224:Cricetinae; D003895:Desmosine / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006603:Hexuronic Acids / Q000032:analysis; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology*; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D007524:Isodesmosine / Q000378:metabolism; D008647:Mesocricetus; D010100:Oxygen / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*
D006603:Hexuronic Acids; D003895:Desmosine; D007524:Isodesmosine; D006821:Hyaluronoglucosaminidase; D010196:Pancreatic Elastase; D010100:Oxygen