Biochemical, clinical, and morphologic studies on lungs of infants with bronchopulmonary dysplasia.

We correlated clinical, biochemical, and morphologic findings in the lungs of 48 infants dying of either bronchopulmonary dysplasia (BPD) or hyaline membrane disease (HMD) to obtain a better idea of the disease process. The infants ranged from 24 weeks of gestation to 1 1/2 postnatal years. The lungs of BPD and HMD infants had higher contents of DNA, alkalisoluble protein, hydroxyproline, and desmosine, as well as increased concentrations of DNA, hydroxyproline, and desmosine when compared with the lungs of 72 control infants. BPD was classified histologically into 4 groups: Group I was a phase of acute lung injury, Group II the proliferative phase; Group III the phase of early repair, and Group IV the phase of late repair. We saw a significant increase in hydroxyproline concentration in Groups II and III. The ratio of type I/III collagen decreased in BPD Groups II to IV. Desmosine was significantly higher only in Group III than in controls. When the pathological classification was related to biochemical and clinical features of BPD, the classification showed dependence on the number of days the infant survived postnatally and not on the gestational age of the infant. The number of days on assisted ventilation was a slightly better predictor of the disease classification than days on > 60% oxygen. A statistical model correctly predicted the pathologic classification 83% of the time.

Cigarette smoke causes rapid lipid peroxidation of rat tracheal epithelium.

Cigarette smoke-induced lipid peroxidation may be an important mechanism of smoke toxicity, but attempts to demonstrate peroxidation of pulmonary tissues after smoke exposure have yielded conflicting results. To examine this question, we exposed rat tracheal explants to whole smoke for 10 minutes followed by air recovery for periods up to 50 minutes (test), or to air alone (controls) and measured conjugated diene levels in the tissue. A dose-related increase in conjugated diene levels was seen in explants exposed to 1, 3 or 6 puffs of smoke. After exposure to 6 puffs of smoke, there was a progressive increase in conjugated diene levels during the first 10 minutes of air recovery; thereafter, test levels remained at about 1.5 times control. Pretreatment of the explants with superoxide dismutase, catalase, or deferoxamine prevented the increase in conjugated diene levels, and inactivation of the enzymes destroyed their protective effect. We conclude that cigarette smoke rapidly produces lipid peroxidation in tracheal segments in vitro, that the severity of the process is directly related to the amount of smoke exposure, and that inflammatory cells are not required for this effect. Lipid peroxidation in this system appears to be mediated by active oxygen species.

Changes of growth hormone, somatomedin C, and bombesin following pneumonectomy.

Left pneumonectomy (PX) was performed on 14-day-old pregnant rats. Serum growth hormone (GH), lung somatomedin-C-like immunoreactivity (SmC), and lung bombesin-like immunoreactivity (BLI), using optimized radioimmunoassays and lung protein concentration (P), were measured 3 h, and 1, 2, 3, 5, and 7 days following pneumonectomy. These levels were compared to two groups of similar animals: sham operated animals and animals not subjected to surgery. Serum GH, lung SmC, and BLI levels were similar in the last two groups of animals, suggesting that surgery had no effect on GH, SmC, and BLI levels. These two control groups were combined and compared to the post-pneumonectomy animals. The post-pneumonectomy animals had significantly higher levels of serum GH at postoperative day 3 and significantly higher levels of SmC at days 2 and 5 without any significant difference in total BLI level and body weight. These results suggest that, first, GH and SmC may play a part in post-pneumonectomy compensatory lung growth and these two may also be interrelated in this response and, second, BLI material(s) perhaps do not play a role in post-pneumonectomy lung growth.

Morphometric and biochemical changes in lungs of growing rats treated with a calmodulin antagonist.

To determine the role of calmodulin in postnatal lung growth and development, 4-week-old rats were injected intraperitoneally on consecutive days with trifluoperazine (TFP), a potent and specific calmodulin antagonist, for a period fo 3 weeks and studied in comparison with normal controls and undernourished weight-matched animals. TFP treatment resulted in stunting of lung growth such that observed normal increments in morphometrically determined total number of alveoli and alveolar surface area and in biochemically determined DNA, elastin, and collagen contents of the lungs were diminished in comparison with age-matched normal controls. However, the TFP treatment also resulted in reduced daily food intake and body weight gain. In the TFP group, lung weight and lung volume were also reduced compared with the weight-matched control group. This resulted in reduced alveolar surface area, total number of alveoli, DNA, collagen, and elastin in the TFP group compared with values in the weight-matched controls. Thus the TFP-induced lung changes were not due to inanition and/or reduced somatic growth. The TFP treatment resulted in reduced activities of calmodulin and cyclic adenosine monophosphate (cAMP)-phosphodiesterase in the lungs of the animals, independent of their nutritional status. Based on these findings, we suggest that calmodulin may be an important regulatory component of postnatal lung growth and development.