Eighteen sheep previously prepared for chronic study were divided into three groups of six animals each. These were given graded inhalation injury utilizing smoke obtained from burning cotton-toweling material. Smoke was insufflated into animals with a modified bee smoker at temperatures less than 40 degrees C. Group H, which received 64 breaths of smoke, showed the most pronounced changes in pulmonary function. The changes consisted mainly of a profound increase in lung lymph flow following a reduced P/F ratio (PO2 in arterial blood/inspired O2 fraction) and an elevation in both thermal and gravimetrically measured extravascular lung water. Similar changes were seen in group M (48 breaths of smoke) and group L (32 breaths of smoke). However, the injury was graded based on the changes in gravimetrically measured lung water and lung lymph flow. These were highest in group H and lowest in group L. These studies confirm our ability to accurately quantitate the injury induced by smoke inhalation. In addition, it demonstrates that lung injury associated with the inhalation of smoke can be graded depending on the duration of exposure.

The purpose of this study was to evaluate lung cell injury during the acute phase of smoke inhalation injury. A group of 10 sheep were anesthetized with halothane and pancuronium followed by endotracheal intubation. In the first experiment 5 sheep were given air (sham group) and 5 were insufflated with cooled cotton smoke with a modified bee smoker. In the second part of our study (Experiment 2) the animals were insufflated with the following number of smoke breaths: 1 x 12 (n = 3); 2 x 12 (n = 4); 3 x 12 (n = 4) 4 x 12 (n = 4); and sham control (n = 1). After 30 min the animals were killed with KCl and the trachea prepared for scanning, transmission electron, and light microscopy. Our initial observation with scanning electron microscopy revealed a large amount of mucus on the surface of the epithelia. Numerous ciliated cells had been sloughed from the epithelium and were observed on the surface of the remaining ciliated cells. The sloughed cells were intact, and the cilia remained on the apical cell surface. Light and transmission electron microscopy revealed that most goblet cells were in the process of extruding mucus. The cytoplasm of goblet and basal cells appeared normal. Ciliated cells had a slightly vesiculated cytoplasm, and many were in the process of being sloughed from the epithelial surface. In these cells desmosomal attachment had been separated. The light microscope evaluation of the tracheal epithelium showed there was no dose-dependent effect between the four treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A bolus of Escherichia coli endotoxin (1.5 micrograms/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

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