Effect of high-dose cimetidine on pulmonary extravascular water after acute smoke inhalation injury.

An animal model utilizing gamma imaging was used to examine pulmonary edema of an inhalation injury model. Tests were conducted using radiolabeled tracers and a dual indicator dilution technique as well as gravimetric analysis of excised lungs to determine extravascular water formation. The effect of cimetidine (Tagamet, an H2 receptor antagonist) was investigated as a potential agent for reduction of pulmonary edema following inhalation injury. Control groups included no treatment; smoke only; fluids only; and smoke and fluids. These were compared with identical groups given the same treatments but with the addition of cimetidine (100-150 mg/kg body weight intravenously). Fluids administered were 5% body weight intravenous infusions of lactated Ringer's solution over two hours. Results show that pulmonary edema was evidenced in animals given an inhalation injury, and was markedly worsened by fluid resuscitation. Treatment with cimetidine at high doses, either before or after inhalation injury, did not protect the animals from formation of pulmonary edema.

Early detection of extravascular lung water in an inhalation injury animal model.

A rabbit inhalation injury model using a dual tracer radioactive isotope technique (Rowland et al., 1986), has been utilized with small- and medium-sized molecular weight tracers. There is oedema formation at 2 h after smoke inhalation or fluid resuscitation and especially with the combination of inhalation injury and fluid resuscitation [corrected]. This oedema appears to have decreased by 24 h post-injury. There does not appear to be any difference between the small- and medium-sized tracers in the transit times of tracer in the lung vascular compartment. The increases in extravascular water volume have been confirmed by gravimetric analyses of the lungs. Thus the pulmonary oedema in the rabbit animal model is detectable within 2 h post-injury, with a return towards normal values some time within 24 h if fluid challenged for short periods. Fluid resuscitation exacerbates the amount of oedema that developed. The onset of pulmonary oedema may therefore be earlier than previously seen clinically, and fluid resuscitation modifications may be of benefit in smoke inhalation injury.

Smoke inhalation model for lung permeability studies.

The purpose of this project was the development of a small animal model and the use of external gamma imaging for the study of acute post-inhalation permeability changes. New Zealand white rabbits were anesthetized with ketamine and acepromazine IM, intubated, and a catheter placed in an ear artery. Smoke was produced by burning absorbent cotton in a combustion chamber supplied with 10 liters/min of air. Smoke was delivered to a holding chamber, allowed to cool to room temperature, and immediately delivered to the animals via endotracheal tube. Animals were allowed to inhale smoke for 3 sessions of 2 to 3 minutes. Blood samples were collected for the measurement of PO2, PCO2, and COHb. Lungs were removed at 3 to 4 days postinjury and subjected to microscopic histologic analysis. The results of six animal experiments showed a significant inhalation injury. The mean COHb level was 48% (range, 36%-58%). The change in the pre- and post-injury PO2 and PCO2 values were not significant (mean PO2, 66 mm Hg; mean PCO2, 32 mm Hg). Histologic evaluation of the lungs of three animals at 24 hrs postinjury revealed extensive loss of tracheal epithelium extended to many terminal bronchi. Inflammation of surrounding tissue, including edema and increased migration of polymorphonuclear cells, was also present. Analysis of tissue obtained at 10 to 14 days showed reparative reepithelialization of trachea and major bronchi but acute inflammation and loss of intralobar bronchi. Inflammatory exudate extended to adjacent alveoli. In conjunction with the above model we have developed a method for the noninvasive measurement of lung permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)