The results of this study indicate that although there have been several animal models of smoke inhalation injury, such as rabbit, dog and goat, this sheep model has many advantages. Sheep were large enough to undergo several surgical and experimental procedures as well as dynamic monitoring of cardiopulmonary hydrostatics and to allow frequent blood sampling for blood gas analysis and biochemical determinations. It is also possible to collect lung lymph from sheep to study the changes of pulmonary fluid and protein exchange after the injury. Moreover, the experiment can be performed while the animal is awake, which should produce reliable data. Furthermore, after smoke inhalation, the sheep had fatal levels of HbCO (>50 percent), decrease in pulmonary compliance, progressive hypoxemia and acute respiratory distress, which are very similar to that found in patients with smoke inhalation. Therefore, this model is useful for further studies of smoke inhalation injury.
Although cyanide intoxication may exist after smoke inhalation, the present study demonstrated that there are two distinct fatal complications: CO poisoning and ARF. In this model, all sheep suffered from CO poisoning (HbCO>50 percent) after smoke inhalation, which supports the concept that CO poisoning is one of the most common complications after smoke inhalation injury. In addition, this study confirms that a high volume of CO in smoke resulted in an increase in HbCO. The longer the smoke inhalation lasts, the higher the HbCO level will be. On the other hand, although all sheep had very high levels of HbCO at the end of smoke inhalation, HbCO decreased quickly after stopping smoke exposure and breathing room air, and returned to normal level (<10 percent) at 6 h postinjury. This is due primarily to the fact that CO is reversibly bound to the heme pigments and enzymes and readily dissociates according to the laws of mass action. It should be pointed out that additional oxygen supply for 5 min after smoke exposure might promote such a decline in HbCO levels.
In this model, another fatal complication after smoke inhalation was ARF characterized by acute respiratory distress, progressive hypoxemia and decreased pulmonary compliance. All sheep that survived CO poisoning had signs, symptoms and laboratory determinations which support the diagnosis of ARF. Almost half (n = 5) of the sheep (n = 12) that were designated to be killed at 24 h postinjury died of ARF during the study period. That the sheep killed at 24 h postinjury had respiratory distress with rates over 40 times/min and Pa02 of 7.1 kPa with existing tracheobronchial pseudomembrane cast and alveolar edema suggests that those sheep would also soon die of ARF. This emphasizes that ARF might follow smoke inhalation and threaten the life of most patients with smoke inhalation.
Of course, the reduced concentration of oxygen in inhaled smoke is one of the causes of early hypoxemia after smoke inhalation. However, the pathologic findings have shown that the main causes of ARF are airway obstruction, atelectasis and pulmonary edema. The atelectasis includes microatelectasis, segmental atelectasis and lobar atelectasis. There may be many factors, such as airway obstruction, disactivation of the surfactants on the surface of alveolar epithelia by chemicals in smoke inhaled, and edematous fluid in alveolar space with subsequent increase in surface tension which may be responsible for the development of atelectasis, but this needs to be confirmed. Pseudomembrane casts existed not only in the tracheo- bronchi, but also in bronchioli of all sheep killed or died after 6 h postinjury, and were the primary cause of five deaths 13-23 h later and was an important cause of ARF in another seven sheep killed at 24 h postinjury. This confirms the clinical finding that airway obstruction is one of the serious events threatening to a patients life after smoke inhalation. Another important cause of smoke-induced ARF is pulmonary edema. That alveolar edema was found as early as 2 h postinjury indicates this kind of pulmonary edema may develop very early after smoke inhalation. This kind of pulmonary edema consists of interstitial edema, alveolar flooding and cellular edema with swelling of alveolar epithelia, as well as capillary endothelia and thickening of alveolar-capillary membrane, which may interfere with the gas exchange process through the membrane itself.
Both polymorphonuclear neutrophil (PMN) infiltration in interstitial space of the alveolar septa and tracheobronchial submucous tissue, and exudation of fluid, proteins and blood cells from capillary lumens into interstitial space at first, then airway lumens through damaged epithelia forming pseudomembrane casts and alveolar space resulting alveolar edema, are the inflammatory responses to smoke inhalation. This results from damage to the tracheobronchial wall and pulmonary parenchyma. There are many physical, chemical, cellular and humoral factors possibly associated with such damage. Heat appears not to play an important role in the injury since the temperature of the smoke inhaled did not exceed 40°C. That tracheobronchial lesions occurred so early (at the end of smoke inhalation) suggests that the chemicals in the smoke, including water soluble gases such as hydrogen chloride, ammonia and sulfur dioxide, and lipid soluble gases such as oxides of nitrogen, phosgeneand aldehydes especially acrolein, might be injurious agents introducing initial or primary impairment of the tracheobronchial tree and lung parenchyma. Certainly, neutrophils trapped in the lungs and many humoral factors such as C3a, PGI2 and TxAa, oxygen- free radicals released or produced after the injury might also contribute to that damage, but are second ary injurious agents.
In summary, as expressed in Figure 7, decreased oxygen content, increased CO, and chemicals in smoke inhaled are three distinctly separate factors triggering serious consequences following smoke inhalation. They can introduce at least two distinct fatal complications: CO poisoning, and acute respiratory failure (ARF). Fatal levels of HbCO, the result of increased concentration of CO in smoke inhaled, is often found after smoke inhalation, but may decrease quickly when stopping smoke inhalation and especially increasing the fraction of inspired oxygen concentration. Although the decreased concentration of oxygen in the smoke inhaled may contribute to hypoxemia, the three causes of ARF, the most common complication following smoke inhalation, are airway obstruction, atelectasis, and pulmonary edema, which might direct ventilatory insufficiency, ventilation-perfusion mismatching, and diffuse injury, and in turn result in progressive hypoxemia. The tracheobronchial lesions and pulmonary damage have the nature of exudative inflammation and are postulated to be produced primarily by the chemicals in inhaled smoke. Of course, many cellular and humoral factors also contribute to the pathogenic process, but are secondary to injury.