ROBERT H. LISS AND JOHN C. NORMAN 
233 
uniformly patient. In micrographs of single 
i alveoli from control dogs, type I and II al- 
veolar epithelial cells, alveolar pores of Kohn 
and alveolar macrophages were identified. Re- 
duction in the diameter and number of pores 
of Kohn in smooth vi^alled alveoli from Group 
III dogs v^as observed. The outlines of erythro- 
cytes in the underlying alveolar capillaries were 
seen in micrographs of control tissue ; scanning 
microscopic observations of lung tissue from 
Group III, continually overloaded dogs differed 
in that RBC's were observed also free in the 
alveoli (Figure 4). 
Physiologic Parameters 
Observed and calculated physiologic values are 
presented in Table II for Dog 6962 (Group III) . 
The data are representative of all dogs in this 
group, all of whom died of acute respiratory in- 
sufficiency six hours after continual infusion 
(100 ml/kg/hr) with lactated Ringer's solution. 
Especially noteworthy are the values for respira- 
tory mechanics, pH, blood gasses, and hemody- 
namic variables ; each changes consistently as an 
index of pulmonary edema. 
Figure 4. — Scanning electron photomicrograph of lung 
tissue from group III (continually overloaded) dogs. 
Erythrocytes (e) are seen free in the alveolus and near 
a pulmonary capillary (c). Open circles define pores of 
Kohn. Mag. X500. 
DISCUSSION 
Controversy persists in regard to the precise 
relation between fluid overload and the genesis 
of acute respiratory insufficiency (ARI).^^ 
Often, patients who have been given large 
amounts of electrolyte solutions in resuscitation 
from low flow states develop an expansion of 
intravascular and interstitial fluid volumes. 
Subsequent edema and congestion may result in 
acute pulmonary insufficiency. 
Clinical studies on the genesis of ARI neces- 
sarily are compromised by therapeutic manage- 
ment of antecedent trauma and shock; thus, 
controlled, pathophysiologic assessment of ARI 
in humans is unlikely since all patients in these 
situations are treated. An alternative, how- 
ever, for understanding the clinical conditions 
may be provided by an animal model of acute 
respiratory insufficiency. The value of this 
canine system is that it provides a clinically 
relevant model of ARI, uncompromised by ther- 
apeutic interventions. i"'^"^ Moreover, the model 
of fluid overloading is relevant to iatrogenic 
acute respiratory insufficiency where infusion 
therapy is used during clinical management. 
In these studies, four groups of animals have 
been investigated. Group I was a control group 
of 3 dogs in which the effects of the experi- 
mental design were evaluated, e.g., anesthesia, 
immobilization, etc. The dogs were not infused. 
Group II, consisting of 6 dogs, was infused in- 
teimittently (50 ml/kg/hr), 25 minutes each 
hour for 6 hours. This schedule of infusion did 
not produce marked ARI ; fluid overloading did 
not exceed diuretic capability, and all dogs 
survived. 
In Group III, both gross and cytopathologic 
alterations in the lung tissue of continually fluid 
overloaded dogs and the accompanying changes 
in respiratory mechanics and hemodynamic 
variables were consistent, co-correlated indices 
of acute pulmonary trauma. Only animals in 
this group showed clinical manifestations of 
pulmonary edema terminally and died after 5-6 
hours of continual infusion with lactated Ring- 
er's solution (100 ml/kg/hr). That continuous, 
massive fluid overloading produced acute pul- 
monary insufficiency was reflected in the in- 
creased transpulmonary pressure, increased 
