762 
PHARMACOLOGY 
Table V. — Results of Hepatic Halothane Metabolism in 
in Miniature Swine 
Alveolar Fraction Metabolic rate Number 
halothane (%) halothane removed (ml/min) Animals 
1.6 ± .05 —.08 ± .07 3 
1.1 ± .04 .05 ± .03 6 
0.6 i .03 .04 ± .04 .30 ± .37 7 
0.25 ± .02 .13 ± .03 .57 ± .16 7 
0.12, 0.09 .03, .32 .10, .56 2* 
0.05 ± .006 .24 ± .05 .13 ± .05 3 
0.01 ± .002 .34 ± .05 .07 ± .004 4 
O.007 ± .006 .59 ± .04 .05 ± .006 4 
0.0026 ± .0003 .... .77 ± .03 .04 ± .009 6 
0.0006, .0004 .... .84, .85 .02, .005 2* 
d= = SE 
* Individual values are presented. 
anesthesia (Table VI), ^ anesthetic removed by 
the liver at or above anesthetic levels was not 
significant. Hov^^ever, as alveolar concentrations 
decreased during the postanesthetic period, 
fraction removed increased to almost complete 
extraction. 
Results of the studies during which animals 
were exposed only to subanesthetic levels dem- 
onstrated that halothane and methoxyflurane 
are metabolized. There was little or no metabo- 
lism of Ethrane, and no detectable metabolism 
of cyclopropane, Forane or nitrous oxide. 
DISCUSSION 
To complete the cardiovascular studies, 63 
days were required from the date of surgery 
through the week after the last anesthetic pe- 
riod. A functional flow sensor, a patent aortic 
catheter, and a healthy animal were required to 
meet this objective. The actual duration of in- 
strumentation averaged 60.6 days with a range 
of 25-127 days. Instrumentation permitted 
measurement of consistent control data in un- 
anesthetized and unmedicated animals which 
then could be compared with those data re- 
corded during anesthesia and postanesthesia. 
Table VI. — Results of Hepatic Fluroxene Metabolism 
in One Animal 
Alveolar 
Fraction 
fluroxene (%) 
removed 
2.18 
—.09 
0.36 
—.09 
0.12 
.42 
0.062 
.42 
0.029 
.74 
0.0098 
.85 
As indicated, there were 48 possible anes- 
thetic study periods. Thirty-eight of the 48 runs 
were accomplished. Six pigs had all 4, 3 had 3, 2 
had 2 and 1 had only 1 evaluation. Incomplete 
periods resulted from aortic rupture subsequent 
to flow sensor implantation in 3 animals and 
nonpatent aortic catheters in 3 animals. 
This instrumentation allowed beat-by-beat 
measurements of cardiovascular variables with- 
out other drug influences. As a result, repre- 
sentative and consistent control data were 
obtained for extended periods. Changes recorded 
during anesthesia were compared to control 
data and provided an excellent means for ana- 
lyzing anesthetic effects on cardiac output and 
related variables. Each anesthetic decreased 
cardiac output, stroke volume, and stroke work. 
Hematocrit was consistently decreased. Heart 
rate, mean arterial pressure, and peripheral 
vascular resistence were variably affected. 
Miniature swine are comparatively resistent 
to rupture of the ascending aorta following flow 
sensor implantation and are excellent animal 
subjects for examining anesthetic effects on the 
cardiovascular system. 
For metabolism studies, miniature pigs were 
surgically implanted as described. Anesthetic 
management during vena cava occlusion was 
difficult as the procedure resulted in severe hy- 
potension. A few animals died during surgery 
at the beginning of the study presumably due to 
severe hypotension. In subsequent animals, 
blood and fluids were administered intrave- 
nously during occlusion of the inferior vena 
cava to maintain arterial pressure near normal. 
This procedure decreased morbidity and mor- 
tality considerably. 
Nine animals were instrumented and the du- 
ration of functional instrumentation averaged 
78 (range 34-150) days. Time required for 
thrombosis of the caval tubing averaged 36 
(range 26-62) days. The portal vein catheter 
was usually the first to become nonfunctional. 
The average time for blood sampling from the 
portal vein was 45 days with a range of 10-105 
days. The number of times animals were stud- 
ied ranged 1-5 with a mean of 3. It was difficult 
to achieve the complete objectives of this instru- 
mentation as the portal vein catheter would not 
