William A. Skornik

Progressive Pulmonary Fibrosis in Hamsters

The concomitant treatment of hamsters with bleomycin and hyperoxia results in a synergistic development of pulmonary injury. We exposed hamsters for 72 hr to 70% oxygen following a single intratracheal instillation of bleomycin (0.16 U/100 g body weight). Groups of 10 animals were killed at 3, 6, 10, 30, 60, 90, and 120 days after instillation for histopathologic and morphometric assessment. Diffuse alveolar damage developed acutely. At 30 days, the intense acute cellular infiltrate had subsided, leaving a focal interstitial pneumonitis. Morphometric quantitation at 10 days revealed that 33.5 +/- 5.3% (x +/- SE) of the lung was diseased; there was apparent healing by 30 days, when 10.5 +/- 2.0% of the lung was diseased. However, progression to diffuse pneumonitis with fibrosis was seen at 60, 90, and 120 days, when 30.2 +/- 4.9%, 38.5 +/- 5.8%, and 38.8 +/- 4.5% of the lung was diseased, respectively. In vivo pulmonary function studies on treated animals at 25 and 55 days showed decreasing dynamic compliance and increased minute ventilation, which corroborates the presence of interstitial fibrosis. We conclude that simultaneous treatment of hamsters with bleomycin and hyperoxia results in interstitial fibrosis with a distribution and progression that mimics human pulmonary fibrosis. This model appears ideally suited for the study of progressive fibrosis and will be useful when development of a widely distributed lesion is crucial.

Corticosteroid treatment of experimental smoke inhalation.

The effect of four corticosteroid analogs was evaluated in the treatment of smoke inhalation injury. Rats were exposed to white pine smoke for 15 minutes at 25 C, in a specially designed smoke apparatus. Methylprednisolone, 10 mg bid × 2d, starting one hour post exposure, was most effective in reducing expectant mortality (22.6%). A single injection of methylprednisolone, 20 mg, at one hour, resulted in a 76.7% reduction. There was no significant difference between the single injection of methylprednisolone and dexamethasone, 4 mg, but the administration of analogs with primarily mineraJocorticoid activity, cortisone and hydrocortisone, actually increased mortality. In the control rats, marked interstitial edema occurred by 24 hours, the absence of which following treatment correlated closely with the results of the mortality study. This suggests that post exposure death due to white pine smoke is a result of direct lung injury, with increased endothelial and alveolar membrane permeability and edema, and that administration of glucosteroids in massive doses was effective in reducing this permeability and resultant edema.

Thermal decomposition products of PVC plastics: effects on guinea pig lung mechanics and pulmonary mixed function oxidase activity

The toxicity of the thermal decomposition products of polyvinyl chloride (PVC) plastic were studied and their pulmonary effects in guinea pigs evaluated. Measures of toxicity included lethality, alteration in lung mechanical function, lung mixed function oxidase enzyme activity and lung organ to body weight ratio. A technical PVC formulation (composition not known) was more lethal than another formulation designed to simulate electrical insulation. Both materials and pure PVC produced highly irritant gases as measured by changes in respiratory rate and compliance (decreased) and total flow resistance (increased). While adverse pulmonary mechanical effects in lung function were observed, lung biochemical parameters were relatively unchanged.

Pulmonary mechanics in guinea pigs: Repeated measurements using a nonsurgical computerized method☆☆☆

Abstract A method of pulmonary mechanics measurement using plethysmography and esophageal pressure to determine tidal volume, compliance, resistance, frequency, and minute volume in guinea pigs is described. The procedure is not surgical, does not require anesthesia, and allows for repeated measurements in the same animals. Calculations based upon physiological data (esophageal pressure as a measure of transpleural pressure and plethysmograph pressure as a measure of tidal volume) are done in real time with a relatively low-cost (

Pulmonary Bacterial Susceptibility in the Burned Rat

12,000) digital computer that displays numerical results as well as stores data for later analysis. The results of this method are compared to the published results of others. Data on repeated measurements in two animals over a 2-week period and the pulmonary effects of exposure to combustion products of plastics at 1, 24, 48 hr postexposure are given.

Eschar: A major factor in postburn pneumonia

An in vivo model system, using the burned rat as a model of altered host resistance, was developed and studied to investigate the lungs ability to handle an aerosolized bacterial insult of either P. aeruginosa or S. aureus. Rates of lung bacterial clearance were correlated with mortality, bacteriologic and histologic results. Susceptibility of the lung to sepsis was shown to be directly related to host resistance and was significantly increased following cutaneous thermal injury. Exposure of burned, non-seeded rats to a bacterial aerosol on day one post burn resulted in a mortality of 50% (P. aeruginosa) and 11.1% (S. aureus). This mortality clearly demonstrates an increased susceptibility at day one post burn. In contrast, this susceptibility gradually decreased with time; no mortality in the burned rat when exposed on day six post burn or in the normal, unburned rat. Histologic findings correlate well with the mortality results showing a gradually decreasing severity of pneumonitis if aerosol exposure was further delayed. Lung bacterial clearance studies revealed that the initial good response of the pulmonary defense mechanisms immediately following aerosol challenge are short-lived and that a marked increase in pulmonary bacterial susceptibility occurs as early as 24 hours following thermal injury.

Pulmonary bacterial defense: Effect of the burn wound on transfer of alveolar macrophage activation in rats by parabiosis☆

Abstract Lung bacterial clearance and mortality studies after a bacterial aerosol challenge together with the determinations of alveolar macrophage function were utilized to assess pulmonary bacterial susceptibility in unburned and burned rats subjected to various grafting procedures. These studies demonstrated that the burned rat is highly susceptible to the development of fatal pneumonitis during the early postburn period. Excision and grafting result in normal bacterial clearance rates and stimulate phagocytosis and intracellular killing by alveolar macrophages present in the lung; however, mortality is not reduced unless an artificial skin is utilized. These studies suggest that burning and grafting result in enhancement of the mechanism by which the lung handles a bacterial challenge but that the effect is short-lived.

Increased airway responsiveness to inhaled methacholine in a rat model of chronic bronchitis.

The alveolar macrophage was studied in parabiotic rats using an inbred strain. Parabiotic pairs were sutured together at five weeks of age. Rats were subjected to a full thickness cutaneous burn of 20 per cent of the body surface area at seven weeks of age, and alveolar macrophages were washed from the lungs at six days post burn. The number of alveolar macrophages, their per cent of activation, and their ability to phagocytize and kill P aeruginosa in vitro were significantly increased at six days post burn in the burned controls and in both the burned and unburned members of the parabiotic pairs. No change in the alveolar macrophages was found in either unburned parabiotic pairs or in those which were sham-burned. These results indicate that a humoral or cellular agent produced either within the cutaneous burn wound or elsewhere as a response to the injury, traverses the parabiotic cross circulation to stimulate the alveolar macrophages.