PATHOPHYSIOLOGIC ASSESSMENT OF A CANINE MODEL 
OF INDUCED ACUTE RESPIRATORY INSUFFICIENCY 
Robert H. Liss and John C. Norman' 
Infusions associated with surgical procedures may 
lead to expansion of intravascular and interstitial fluid 
volumes. When pulmonary edema and congestion ensue 
acute respiratory insufficiency (ARI) may result. To 
assess the magnitude of fluid overload necessary for 
ARI production, 20 mongrel dogs were infused with 
normal saline: I) untreated controls; II) intermittently, 
50 ml/kg/hr; III) continuously, 100 ml/kg/hr; IV) con- 
tinuously, 100 ml/kg/hr with furosemide (0.8 mg/kg) 
every two hours. Scanning/transmission electron micros- 
copy, light microscopic and physiologic assessments were 
made of pulmonary tissue. Ultrastructural and patho- 
physiologic correlates of ARI were seen only in group III 
(continually loaded, no furosemide). Scattered areas of 
pulmonary pathology included edema i.e., intra-alveolar, 
granular precipitate and widening of alveolar septa. 
Congestive changes were dilated alveolar capillaries, 
distended intra- and inter-membranous spaces, basement 
membrane spreading, hypertrophic and cuboidal epithe- 
lial cells, capillary rhexis and alveolar hemorrhage, 
RBC's and hemosiderin-filled macrophages in alveolar 
spaces. Pulmonary tissue ultrastructure and pathophys- 
iologic data from groups I, II and IV were within nor- 
mal limits. The combined data indicate that massive, 
continuous fluid overload (100 ml/kg/hr for 4-6 hrs) is 
required to produce ARI in normal dogs; associated cy- 
topathology is essentially indistinguishable from that 
observed in "shock lung." 
INTRODUCTION** 
Acute respiratory insufficiency (ARI) has be- 
come an increasingly frequent cause of death 
following trauma, shock or sepsis.^ Patients may 
survive initial hemodynamic insults only to 
develop a progressive, irreversible pulmonary 
insufficiency. The importance of recognizing the 
early pathophysiologic events in the genesis of 
respiratory failure is reflected in the number 
of model systems designed to study its develop- 
ment. Experimental acute respiratory and 
hemodynamic changes have been investigated 
* Department of Surgery, Harvard Medical School, Boston, and 
Arthur D. Little, Inc., Cambridge, Massachusetts. 
** Supported, in part, by The John A. Hardford Foundation, The 
John and Mary R. Markle Foundation, The Charles E. Merrill Trust, 
and U.S.P.H.S. Grant No. HE 14294. 
after trauma and post-surgical shock,^'^ hemor- 
rhagic shock,'*'^ septic shock," injection of free 
fatty acids,' and pump-oxygenator procedures.^ 
Each of these models has been useful in eluci- 
dating the sequence of events in the experi- 
mental production of pulmonary insufficiency. 
However, in the last two decades, few studies 
have been initiated to investigate the role of 
fluid overload in the genesis of ARI."-^- 
In order to assess the magnitude and patho- 
physiologic significance of fluid overload in the 
production of acute respiratory insufficiency, 
an investigation of the eff"ects of continuous 
fluid infusion on pulmonary function and struc- 
ture has been undertaken. This report cor- 
relates the pathologic observations with an 
extended series of measured and derived 
respiratory and hemodynamic data. 
MATERIALS AND METHODS 
Normal mongrel dogs weighing 26 ± 1 (SEM) 
kg, were anesthetized with sodium thiamylal 
(Surital, Parke Davis). Fluid overload was ef- 
fected by infusing lactated Ringer's solution; 
the experimental protocol is summarized in 
Table I. 
Parameters of respiratory mechanics and the 
work of respiration were calculated from data 
on inspiratory and expiratory air flow and 
transpulmonary pressure. A Respiratory Ana- 
log Computer (Division of Experimental Sur- 
gery, Naval Medical Research Institute) was 
used to calculate and display tidal volume and 
work of breathing for each breath. Lung com- 
pliance was calculated by dividing inspired 
volume by the difference in transpulmonary 
pressure at each inspiration and each expira- 
tion. Transpulmonary pressure was measured 
as the differential of tracheal air pressure and 
intraesophogeal pressure. Other relevant phys- 
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