760 
PHARMACOLOGY 
each anesthetic period. Arterial blood samples 
were obtained to establish control blood gas val- 
ues. 
For 2 weeks prior to surgical instrumenta- 
tion, animals were brought to the laboratory 
from their outside pens and placed on a table 
for 10-20 minutes. This procedure allowed them 
to adapt to the laboratory environment and per- 
sonnel. During the postoperative period, the 
same procedure was followed. As a result, when 
control recordings of cardiovascular variables 
were made, animals rested quietly on the table. 
Four anesthetics were used in this study : hal- 
othane, methoxyflurane, pentobarbital sodium 
and thiamylal sodium. The experimental design 
was to administer each of the 4 anesthetics at 2 
week intervals to 12 animals. Ideally, this would 
result in 48 anesthetic periods. During each pe- 
riod, anesthesia was induced with the drug to 
be studied and a 1 hour equilibration period fol- 
lowed. Spontaneous ventilation was assisted by 
manual compression of the rebreathing bag. 
The following 2 hours were used to determine 
the effects of each anesthetic on cardiac output 
and related variables. Assisted spontaneous 
ventilation was provided during study periods. 
Administration of an anesthetic was discon- 
tinued 3 hours after induction. Variables were 
recorded at 15 minute intervals during anes- 
thesia and 1, 2, 3, 24, 96 and 144 hours post- 
anesthesia. 
For metabolism studies, Hormel swine, 35-45 
kg, were selected.* These animals were condi- 
tioned to the laboratory environment as de- 
scribed previously. During surgical anesthesia 
with halothane, nylon intravascular catheters 
were implanted to permit later sampling of 
blood from the aorta, portal vein and common 
hepatic vein following recovery from surgery. 
Silastic tubing was secured to one end of the ny- 
lon catheter. The portal vein was cannulated 
with the Silastic portion via the splenic vein. A 
common hepatic vein was constructed using a 
modification of the method of Vetto and Boge.^ 
A 2-cm section of Tygon tubing with catheter 
attached was implanted in the inferior vena 
cava 1 cm anterior to the renal veins. The slow 
formation of a clot in this tubing isolated the 
upper inferior vena cava, creating a common 
hepatic vein. The slow clotting permitted the 
development of collateral venous pathways pos- 
terior to the tubing via the vertebral and azygos 
veins. Between the right atrium and the oc- 
cluded tubing, blood entering the vena cava 
flowed from the major and minor hepatic veins, 
since the phrenic veins had been ligated during 
the surgical procedure. The catheter tip at- 
tached to the Tygon tubing was placed at the 
level of the major hepatic veins. Catheters were 
implanted in the abdominal vena cava and aorta 
via the femoral vein and artery. During the post- 
operative period, indocyanine green dye was 
injected through the femoral-vein catheter and 
blood was sampled from the common hepatic 
vein. When no dye was immediately detected in 
blood from the hepatic vein, we concluded that 
complete thrombosis of the caval tubing had oc- 
curred. Thrombosis occurred 26-62 days post- 
implantation. 
Studies were conducted after occlusion of the 
caval tubing. Halothane was administered to in- 
duce anesthesia and measurements were made 
after alveolar concentrations had been held con- 
stant for 45-60 minutes at 3 different levels.^ 
Thereafter, control of alveolar concentrations 
were discontinued. Blood samples from the por- 
tal vein, aorta and common hepatic vein were 
obtained simultaneously from unmedicated ani- 
mals. The volume of anesthetic in hepatic ven- 
ous blood divided by the total inflow volume 
yields the minimum fraction removed by the 
liver, and this fraction was defined as anes- 
thetic metabolized. 
In a similar study,*' animals were exposed only 
to subanesthetic concentrations to demonstrate 
the extent of hepatic metabolism of halothane, 
methoxyflurane, cyclopropane, Ethranefff (2- 
chloro-1, 1, 2-trifluoroethyl difluoromethyl 
ether), Foraneftt (l-chloro-2, 2, 2-trifluoro- 
ethyl difluoromethyl ether) and nitrous oxide. 
After establishment of equilibrium, fraction 
of anesthetic removed by the liver was de- 
termined. 
RESULTS 
Data obtained from cardiovascular studies 
are presented (Tables I-IV).^ After halothane 
ttt Trademark, Ohio Medical Products, Division of Air Reduction 
Company, Inc. 
