THE EFFECT OF DIMFTHYL SULFOXIDE 
ON THE CARDIOVASCULAR SYSTEM OF CATS 
by 
Maureen E. ,atman 
Submitted in Partial Fulfillment of the Requirements 
for the Degree of 
Master of Science 
in the 
Eiological Sciences 
Program 
- - 
8/10 /s 3 - 
Advi Date 
/ 
.->dL m. at c I&, - ,953 
Dean of the Graduate School 9a.t e 
- - 
YOUNGSTGlrDJ STATE UNIVERSITY 
ABSTRACT 
THE EFFECT OF DIMETHYL SULFOXIDE 
ON THE CARDIOVASCULAJ? SYSTEM OF CATS 
Maureen E. Altman 
Master of Science 
Youngsto~vn State University, 1983 
Diastolic pressure (DP), systolic pressure (SP), 
pulse pressure (PP), mean arterial pressure (MAP), central 
venous pressure (CVP), heart rate (HR), and. the R and T 
wave amp1itud.e~ iK:ere measured to determine the effect of 
intravenous d.imethy1 su1foxid.e (DMsO) on the card.iovascular 
system of anesthetized cats over a 15 minute period. A 
statistical analysis (t-test for paired comparisons) re- -- 
vealed a significant effect of the drug on all of these 
variables. An increase in the R and T 1:Tave amplitude som 
after administration of the drug 1vas indicative of a direct 
effect on myocardial cells. The HR and MAW decreased rapidly, . 
and the CVP became elevated. As the homeostatic mechanisms 
- -- 
of the body compensated, the HR gradually returned to normal, 
while the MAP eventually became significantly elevated and 
remained so until the end of the experiment, probably due to 
increased cardiac output. 
The author wishes to express her sincere thanks to 
her adviser, Dr. James Re Toepfer, for his encouragement 
and guidance throughout the course of this research. 
-Thanks to Dr. David E. MacLean for sharing his 
knowledge and time for the statistical analyses. 
Thanks to Dr. Dale 17. Fishbeck for his advice, 
faith and encouragement. 
iv 
TABLE OF CONTENTS 
PAGE 
ABSTRACT....... . ............. ii 
ACKNO1,'lLEDGEMENT S . . . . . . . . . . . . . . . . . iii 
TABLEOF CONTENTS . . . . . . . . . . . . . . . . iv 
LIST OF ABEREVIATIONS . . . . . . . . . . . . . . V% - 
LIST OF FIGURES . . . . . . . . . . . . . . . . . ~3-i 
LISTOFTABLES ... . ovtii 
CHAPTER 
I. INTRODUCTION . 1 
11. MATERIALS Al!TD METHODS . . . . . . . . . . 7 
Animals. . . . . . . . . . . . . . . . . 7 
Drugs and Solutions . . . . . . . . . . . 7 
Equipment. . . . . . . . . . . . . . . . 8 
Anesthesia . . . . . . . . . . . . . . . 9 
- - 
Surgical and. Experimental Procedure . . . 10 
Measurement of Data . . . . . . . . . . 12 
- 
111. RESULTS . . . . . . . . . . . . . . 13 
Descriptive Analysis . . . . . . . . . . 13 
Mean Arterial Pressure . . . . . . . . 42 
Central Venous Pressure . . . . . . . . --4 2 
T IT!ave Magnitude . . . . . . . . . . . . . 44 
-~ 
Pearson Correlation . . . . . . . . . . . 45 
.- 2- 
v 
TABLE OF CONTENTS (Continued) 
PAGE 
IV . DISCUSSION ......em...e... 48 
.................... APPENDIX 54 
BIBLIOGRAPHY ............~..... 103 
LIST OF ABBREVIATIONS 
ABBREVIATION DEFINITION UNITS 
C. 0. Cardiac output 
b~m Beats per minute 
CVP Central venous pressure mmHg 
DMSO 
DP 
ECG 
HR 
IV 
MAP 
Max 
Min 
PP 
R to R interval 
R wave 
S. E. 
SF 
SV 
TPR 
Time 
T wave 
Dimethyl sulfoxide 
Diastolic pressure mmHg 
Electrocardiogram 
Heart rate bpm 
Intravenously 
Mean arterial pressure mmHg 
Maximum 
l?ini mum 
Pulse pressure mmIig 
- - 
Dist,mce between R nave peaks mms 
ECG deflection corresponding mvs 
- 
to ventricular depolarization 
Standard error 
Systolic pressure mmHg 
Stroke volume -- 
Total peripheral resistance 
minutes: seconds 
ECG deflection corresponding 
to ventricular repolarization 
Volume per volume 
- A 
LIST OF FIGURES 
FIGURE PAGE 
1 . Graph o f Mean M.AP (+ S. E. ) vs. Time . . . . . . . . 29 
- 
2. Graph of Nean CVP (+S.E.) vs. Time . . . . . . . . 30 
- 
3. Graph of Mean HR (+S.E.) vs. Time . . . . . . . . 31 
- 
I$. Graph of Mean R !'iave Nagnitude (+s.E.) vs. Time . 32 
- 
5. Graph of Mean T :'lave Nagnitude (+s.E.) vs. Time . 33 
- 
TABLE 
LIST OF TABLES 
PAGE 
.... 
1 . Statistics for Control and . Treatment MAP 14 
2 . Statistics for Control and Treatment CVP .... 17 
3 . Statistics for Control and . Treatment HR ... 20 
4 . Statistics for Control and Treatment R la!ave 
................... Magnitude 23 
5 . Statistics for Control and Treatment T !7ave 
Magnitude ................... 26 
...... . . 6 T-Test for Paired Comparisons: DP 34 
....... 7 . T-Test for Paired . Comparisons: SP 35 
....... 8 . T-Test for Paired . Comparisons: PP 36 
...... . 
9 T-Test for Paired Comparisons: MW 37 
...... . 10 T-Test for Paired Comparisons: CVP 38 
. . 
. ...... . 11 T-Test for Paired Comparisons: HR 39 
12 . T-Test for Paired . Comparisons: R Magnitude . . 40 
. 
13 .. T-Test for Paired . Comparisons: T l4agnitud.e . . 41 
• .............. 14 Pearson Correlation 47 
INTRODUCTION 
Dimethyl sulfoxide is a relatively new and very 
controversial drug. In recent years it has been hailed as 
a 1lmiracle drugv and the long awaited cure for arthritis. 
This derivative of lignin and by-product of the paper - 
industry so far has proven extraordinary and diverse, and 
much work is currently in progress to further explore its 
potentials. Its analgesic, antiinflammatory, antiedamatous 
and bacteriostatic properties have made it a valuable tool 
of the veterinary profession. Use by physicians in the 
United States has only been approved for treatment of 
interstitial cystitis, although it is used extensively 
throughout Eurasia. 
This research attempts to establish a pattern be- -- 
tween the intravenous injection of DMSO in the anesthetized 
cat and the resulting effects on the cardiovascular syste& 
namely the MAP, CVP, HR, and R and T wave amplitudes. The 
latter three are obtained from electrocardiogram (ECG) 
analysis. 
-- 
A brief background of the chemical and pharmaco- 
logical properties of DMSO is necessary for a more complete 
understanding of its actions. First of all, DMSO is a 
prominant member of the family of polar but aprotic sol- 
-~ 
vents, being extremely versatile because it can act as a 
- -- 
nucleophilic reagent at either the oxygen or sulfur terminal. 
Its structure can be visualized as a tetrahedron: 
P 
CH3-d-CH3 0. 
The compound's polar nature, capacity to accept 
hyd.rogen bond.s, and small, compact structure result in its 
ability to associate with water, proteins, carbohyd.rates, 
nucleic acids, ionic substances and. other constituents of 
living systems. This combination, as theorized. by Szmant 
(1975)~ may be related. to its ability to penetrate living 
tissues without causing significant damage. 
Klingman (1965), using varying concentrations of 
DMSO, demonstrated its ability to easily cross most mem- 
branes (except nails and tooth enamel) by a reversible 
process. The integrity of the membranes appeared unaf- 
fected, except when very concentrated (90-100%) doses 
- - 
came in direct contact sith the membrane, Rapid movement 
and generalized distribution of DIiISO into nearly every 
- 
tissue of the body was shown by Denko et ale (1967), 
Gerhards and Gibian (1967)~ and Kolb et al. (1967). 
This penetrating ability makes it a useful vehicle 
for many d.rugs, often enhancing their actions. For ex- - 
ample, Klingman (1965) mixed dyes and 5teroid.s with DMSO 
and. reported. enhanced. penetration through human skin. It 
has also served. as a carrier to treat viral infections, 
such as herpes simplex in man (~shton et al., 1971) and 
feline panleukopenia (Dalce, 1967), and certain cancer 
chemoth%-apy models (Elzay, 1967). But because of this 
carrier effect, care must be ta.ken ahen determining the 
dosages of drugs used in conjunction with DIISO, especially 
those affecting the cardiovascular and central nervous 
systems (Upson, 1980). 
For example, nhen Smith et a-1. (1967) injected 
DPISO IV into unanesthetized cats, the LD 50 \?:as approx- 
imately 4 g/kg; but, in experiments by ~i~tefa'o and. Iilahn 
in 1965 with cats anesthetized using a barbituate -urethane 
solution, the LD 50 aas'less than 0.4 g/kg. Rabbits 
anesthetized with sodium pentobarbital required only 
1.8 g/kg of DMSO IV as a lethal dose (Domer et al,, 
1977), 
while 19.2 g/kg was required to kill unanesthetized rab- 
- - 
bits (Caujolle et al., 1967). 
Cardiovascular effects of DMSO sere examined by 
- 
Klingman ( 1965), who found topically applied DMSO to be 
a potent histamine-releasing agent, Histamine has a 
vasodilating effect on the arterioles and increases cap- 
illary porosity. This permits leakage of both fluid and - 
plasma proteins between the blood vessels and the tissue&. 
In a study by Bradham and Sample (1967) involving topical- 
DMSO application in dogs, the plasma volume showed a mean 
decrease of 6.476, and in another experiment the extra- 
cellular fluid showed a mean decrease of 4,376. - -. 
The nature of the cardiac inotropic response to 
DMSO is highly variable in the literature researched. 
In 
experiments by Spilker in 1972, cat and dog myocardium 
exhibited only inhibited contractile strength in response 
to very modest concentrations of DMSO (O.O7M), while 
Shlafer and Karoa (1975)~ using rat and guinea pig myo- 
cardium, found concentrations of 0.7T4 or below produced 
positive inotropy. DMSO appears to alter the myocardial 
contractile strength by several mechanisms, including 
osmotic stress placed on the myocardial cell (Shlafer 
and Karovr, 1975), a change in membrane permeability to 
nater and electrolytes (Franz and Bruggen, 1967), and 
changes in enzyme activity (Rammler, 1967;,Burges et ale, 
1769) 
- - 
In vivo experiments examining the effects on 
chronotropy produced variable results also. Using 
- 
anesthetized cats, DiStefano (1965) found the IIR fell 
transiently immediately after administration of DNSO IV 
(200 mg/kg), but returned to normal values within five 
minutes. PBterson and Robertson (1967)~ hoeever, mcorde-d 
an increase in HR of approximately 20-30 bpm at 5000 mg 
and 10,000 mg DMSO IV to anesthetized dogs. After injecting 
1.1-3.3 g/kg DI4SO IV to anesthetized cats, Spilker (1972) 
observed a trcansient increase in HR, follov~ed by a decrease 
- - 
for one or tao minutes, then a return to control level. 
Blood, pressure experiments also yield.ed. variable 
results. DPISO vas administered IV to anesthetized cats at 
200 mg/kg at 15 minute intervals by DiStefano in 1965. At 
a cumulative d.osage of 1 g/kg, the increment vras d.oubled.. 
The blood. pressure fell transiently imrned.ia.tely after 
administration, and. returned to normal within five minutes. 
The repeated IV administration mhere each dose nas doubled 
led to grad.ually lowered. blood. pressure, until d.eath at 
4 g/kg. 
In another experiment using anesthetized cats, 
Spilker (1972) injected 1.1-3.3 g DMSO/kg and obtained a 
biphasic response. A transient increase was followed by 
prolonged blood pressure depression. It returned to 
control level in dne to two minutes, then became slightly 
- - 
elevated. 
In a study involving brain edema reduction by 
- 
Camp et al. in 1981, a transient increase in CVP mas 
observed after DNSO administration. This increase peaked 
at five minutes, then returned to normal. However, this 
result was khought to be due to the large volume of-10% - 
DMSO solution injected (approximately 27 ml to a 3 kg 
rabbit). I'lhen Del Bigio et al. (1982) injected the 
same dosage over a three hour interval, no significant 
change in CVP was noted. 
- -- 
Since several of the above experiments demonstrated 
a variablity of response to DTvISO , this research was 
und.ertaken using carefully controlled, experimental con- 
d.itions and. using a large number of repiicated trials. 
In ad.d.ition, to evaluate the total cardiovascu1a.r response, 
multiple parameters were examined simultaneously. 
MATERIALS AND METHODS 
Animals 
Thirty-two healthy cats of varying age, sex, and 
weight were rand.omly selected., then paired accord.ing to 
sex and. weight. One member of each pair lxas d.esignated 
a control, the other an experimental (DMSO-treatment) 
animal. The control and, experimental groups each consisted 
of eleven females, two males and. three neutered. males, 
All cats were fed. commercial dry cat food, and supplied 
with fresh water 9 libitum. 
Drugs and. Solutions 
Normal saline (0.9%) was used. either for injection 
- - 
or as a medium for other solutions. This solution was 
sterilized and, kept refrigerated., but was warmed to room 
- 
temperature at least one hour before use, Fresh solutions 
were prepared ~veekly. 
Sodium citrate solution, used in the blood pressure 
detection apparatus, was prepared by dissolving 10-g of - 
sodium citrate crystals per liter normal saline. 
Heparin, used as the anticoaggulant, was prepared 
by dissolving 50 mg heparin per milliliter normal saline. 
DMSO solution was prepared by diluting one part - 
- -- 
DMSO (1.100g/ml) to one part sterile normal saline to 
obtain a 50:50 v/v solution for injection. 
Methoxyflurane  meto fane--Pitman-Moore) was the 
inhalant anesthetic used during the experiments. The 
principal response to the drug is central nervous system 
d.epression and. skeletal muscle relaxation. Light anes- 
thetic d.epth mas maintained. by monitoring respiratory 
rate and skeletal muscle relaxation. This level of 
anesthesia had. no noticeable affect on card.iovascular 
parameters, and, correlates most closely with plane ii 
of ether anesthesia. 
Equipment 
Two Gilson table- top Polygraphs (Mo d.el #ICT-5H) 
were used. for the experiments. One recorded the MAP, 
CVP, and. ECG at a chart paper speed, of 2.5 mm/sec. The 
- - 
other record.ed, the ECG at 10 mm/sec. The machines were 
turned. on at least 10 minutes prior to use to ensure 
- 
proper warm-up. 
Stand.ard, lead. I was used for record.ing the ECG. 
The positive record.ing need.le e1ectrod.e was placed. in the 
upper left -thoracic v~all, the negative recording electrode 
in the upper right thoracic wall, and the ground electrode 
was placed in the ventral abdominal wall. These three 
electrodes then connected to the respective leads 
of the ECG chaanels from each polygraph. 
The MAP and CVP were each measured using a separate - 
blood pressure apparatus. Each apparatus consisted of a 
sodium citrate-filled. reservoir fitted with a calibrated. 
pressure gauge and. a pressure bulb. This reservoir was 
connected via a 3-way valve to a Stratham P23AA pressure 
transducer and. to a PE 50 polyethylene tube which, turn, 
was attached. to a ca.theter inserted into a blood. vessel. 
The 3-vray valve was used. to select one of three important 
functions: (1) calibration, (2) sodium citrate flush of 
the catheter tip, and. (3) record.ing of blood. pressure. To 
calibrate, the 3-~1ay valve was set so that the reservoir 
was connected to the pressure transducer. Thus, knovm 
pressures could be recorded on the Polygraph by using the 
pressure bulb and pressure gauge. The MAP channel sensi- 
tivity could then be adjusted so that 200 mmHg pressure 
(as indicated by the gauge) resulted in a 4 cm pen deflec- 
- - 
tion. To flush the catheter tip (to prevent clotting) the 
3-way valve was set so that the reservoir vas connected to 
the catheter. Pressure aas then increased in the reservoir 
using the bulb so that sodium citrate could be forced into 
the catheter tip. To record blood pressure, the 3-way 
valve was set so that the catheter was connected te- the - 
pressure transducer. The pressure could then be recorded 
by the Polygraph. 
Anesthesia 
Each cat mas weighed to the nearest 10 gm, then 
- - 
anesthesia was induced with Metofane by inserting the 
head into a plastic chamber attached to a Connel 201 
Anesthetic Machine. After induction, an endotracheal tube 
was inserted and the cuff inflated.. This tube was then 
attached. to the anesthetic machine and. the amount of 
Meto fane delivered to the animal nas adjusted throughout 
the experiment to maintain a constant plane of anesthesia. 
An oxygen flow regulator, connected. to the anesthetic 
machine, was ad,justed to deliver 15 ml 02/kg body weight. 
Suction was applied. as necessary to remove excess fluid, 
from the lungs and. air-passage mays. 
Surgical and Experimental Procedure 
Hair was clipped. from the right and. left med.ia.1 
thighs and from the ventral neck region. The left femoral 
- - 
vein, right femoral artery, and left jugular vein 
dissected free from surrounding fascia, blood vessels 
- 
and nerves. The femoral vein and artery were cannulated 
using Abbocath-T, 20-gauge, 3.2 cm IV catheters (Abbott). 
The catheters aere tied to the blood vessels to prevent 
chance dislbdgement. The venous catheter was fitte'd with- 
a male adapter plug (Abbott), to be use
d 
as an injection 
portal. The arterial catheter was attached. to the poly- 
ethylene tubing of the pressure transd.ucer for MAP 
measurements. The jugular vein was catheterized. using -~ 
- -- 
a Venocath-18, 28 cm IV catheter (~bbott) for CVP measure- 
ments. This catheter was advanced until the tip was just 
superior to the opening of the right atrium, as determine
d 
by: (1) measurement of the d.istance to the heart as 
determined. by palpation of the heart beat, (2) the slight 
resistance felt on the catheter when the heart mas actually 
entered, and (3) the recordings on the CVP channel. 
If, 
by chance, the ventricle was entered, the pressure became 
noticeably greater, and the catheter was then withdrawn 
until these pressures disappeared. After the conclusion 
of several of the experiments, the animals were dissected 
and the catheter was noted, always to be correctly positioned.. 
Immediately after catheterization was complete, 
heparin (5 mg/kg) vras injected into the femoral port'al 
and then forced into the circulation, as were all inject- 
ions, with an injection of 0.2 ml saline. 
- - 
The arterial and jugular catheters sere flushed 
~rith sodium citrate solution from their respective res- 
- 
ervoirs, and checked for clots. Needle electrodes ?!ere 
attached in lead I position by insertion through the skin, 
and sample MAP, CVP and ECG recordings were made. The MU 
and CVP calibrations were checked and the catheterz flushed 
once more. YIhen the tracings stabilized, either 1.0 ml/kg 
of sterile saline solution (control) or 1.0 ml/kg of DIISO 
(experimental) vras injected into the venous portal. Event 
markers on both Polygraphs sere depressed at the beginning - 
- -- 
of the injection (time O), and were released upon com- 
pletion. of the injection. In this manner an accurate 
record.ing of the injection time was obtained.. At the end. 
of the experiment (15 minutes), the MAP and. CVP calibrations 
were once more checked. to make sure of the record.ing stab- 
ility. The cat vas then euthanized.. 
~ea2rement of Data 
Values for the DP, SP, PP, MAP, CVP, HR, R and T 
waves are tabulated in the appendix. DP and SP values, 
in mmHg, were measured directly from the traces. PP was 
calculated using the formula PP=W - E-P. MAP values 
obtained from the formula MAP=DP + 1/3(PP). 
Increased precision of measurements was obtained 
by using a dissecting microscope (7X magnification) with 
a calibrated ocular scale. The CVP trace often fluctuated 
- - 
due to respiratory and heart-induced pressures, so the 
value recorded was an average. 
- 
The HR, in bpm, was calculated using the formula 
HR=GO/(R to R interval)/chart paper speed. The R to R 
interval was measured with the aid of the dissecting 
microscope,-and the chart paper speed was 10 mm/seand. - 
R and T wave magnitudes were taken from the ECG 
recorded at 10 mm/second. Again, the microscope was used 
to increase accuracy. The values were recorded in mvs. 
T waves could be positive or negative, and were occasion- 
- 
ally diphasic. If the later was the case, the height of - -- 
the tallest peak was recorded. 
RESULTS 
Descriptive Analysis 
The mean, minimum, maximum, range, standard. error 
and variance are presented. in Tables 1-5. for MAW, CVJ?, HR, 
R-wave magnitud.e and. T-wave magnitude for each of the 63 
time peri0d.s measured. Missing values were eliminated. 
from the calculations. In ad.d.ition, graphs of the mean 
values (+s.E.) for each of these variables against the 
- 
independent variable time are plotted. in Figures 1-5, 
respectively. 
A two-tailed t-test for paired comparisons was used 
to analyze each of the above variables as well as the DP, 
SPY and PP.at the time of maximum effect (ta) and at the 
- - 
end. of the experiment (tb). The data and. the results of 
the statistical analyses are presente
d 
in Tables 6-13. 
- 
For this analysis, the animals were paired. by sex and., 
as closely as possible, by weight. Each pair, consisting 
of an experimental and. a control animal, was assigned 
to one of 16-blocks. The t-test was performed using the. 
difference between the values at time 0 and ta or tb, so 
that normal variations among control and. treatment animals 
did not affect the results. Missing values were estimated. 
using the method, of Yates as d.escribed, in Steel and -. 
- -- 
Torie (1960). 
TABLE 1.--Statistics for Control and. Treatment MAP (mrnHg) 
N= 16 Unless Otherwise Indicated. 
Control Data Analysis 
TIME 
00 : 00 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00:22 
00: 24 
00: 26 
00:28 
00: 30 
MEAN 
80.8 
81.1 
81.2 
82.0 
81.8 
8 1.2 
80.2 
80.4 
80.7 
80.5 
80.5 
80.4 
80.7 
80.7 
80.5 
80.6 
80.8 
80.9 
81.1 
81.0 
80.7 
80.9 
81.2 
80.6 
80.9 
81.1 
80.8 
80.6 
80.4 
80.7 
81.3 
76.3 
81 05 
81.0 
81.3 
81.4 
81.6 
81.7 
81.5 
81.6 
81.0 
81.1 
MIN 
55.7 
55.7 
55.7 
55.7 
56.0 
53.7 
55.0 
55.0 
54.0 
55.0 
54.7 
54.7 
55.0 
54.7' 
55.0 
55.0 
55.7 
55.3 
55.0 
56.0 
54.0 
55.0 
55.0 
55.0 
55.7 
54.7 
54.7 
54.7 
54.7 
55.0 
54.7 
53.7 
53.7 
53.0 
52.7 
52.0 
52.0 
51 07 
50.0 
49.7 
49.7 
50.0 
MAX 
--- 
RANGE 
101.3 
100.6 
102.6 
101.3 
101.7 
104.6 
102.3 
103.7 
104.7 
103.3 
104.0 
104.0 
103.0 
102.0 
192.3 
103.3 
100.6 
101.0 
103.0 
101.7 
103.7 
102.7 
103.0 
100.7 
101.3 
103.3 
101.6 
100.6 
102.3 
101.7 
101.6 
70.3 
103.3 
104.3 
103.3 
104.3 
102.7 
104.6 
105.3 
103.0 
102.0 
101.7 
-- - -- 
S.E. 
-7xK 
7.003 
7.020 
6.987 
7.017 
7.055 
6.991 
6.971 
7.124 
7.041 
7.054 
6.945 
6.994 
6.938 
6.933 
6.943 
6.886 
7.018 
7.074 
6.984 
6 909 
7.061 
7.116 
6,895 
7.017 
7.131 
7.086 
6.953 
7.014 
6.999 
7.070 
2: ;A; 
6 945 
6.974 
7.084 
6.868 
6.985 
6.870 
6.918 
6.776 
6.727 
VARIANCE 
*N= 15 observations 
TABLE 1 .--Continued 
TIME MEAN MIN MAX 
DMSO Treatment Data Analysis 
RANGE 
99.0 
100.3 
100.7 
100.6 
102.0 
103.7 
106.4 
104.4 
106.6 
107.0 
107.3 
109.0 
108.7 
109.0 
109.7 
109.0 
11 1.0 
111.3 
110.0 
111.4 
110.3 
71.7 
72#6 
74.3 
75.0 
70.0 
56.3 
57.4 
57.6 
58.3 
59.6 
64.6 
64.0 
65.4 
66.0 
71.4 
71 .O 
73.6 
81.3 
81.0 
85.4 
89.3 
91.6 
93.0 
VARIANCE 
TABLE 1.--Continued 
VARIANCE 
TIME MEAN MIN MAX 
1 12.0 
113.0 
111.7 
111.7 
1 12.0 
122.7 
111.3 
108.7 
114.7 
114.7 
112.7 
112.7 
108.3 
109.3 
106.3 
110.7 
110.3 
135.0 
118.7 
RANGE 
*N= 15 observations 
17 
TABLE 2.--Statistics for Control and. Treatment CVP (mmHg) 
N= 16 Unless Otherwise Indicated. 
Control Data Analysis 
TIME MEAN 
O0:OO 0.9 
00:02 1.1 
00~04 1.4 
00:06 1.5 
00:08 1.6 
00: 10 1.6 
00: 12 1.5 
00: 14 1.5 
00: 16 1.4 
00:18 1.4 
00:20 1.4 
O0:22 1.4 
00~24 1.4 
00~26 1.3 
00:28 1.3 
MIN MAX RANGE 
*N= 15 observations 
18 
TABLE 2. --Continued. 
TIME MEAN MIN MAX 
04:30* 0.8 -0.5 2.5 
05:00* 0.7 -1.2 2.5 
05:30 
0.6 -1.2 2.5 
06:OO 0.7 -1.5 2.5 
06:30 0.7 -1.0 3.0 
07:oo 0.6 -1.5 3.0 
07:30* 0.6 -1.7 3.0 
08:OO 0.7 -1.5 3.0 
O8:30 0.7 
-1.0 2.7 
09:OO 0.6 -1.5 3.0 
09:30 0.6 
-0.7 3.0 
1O:OO 0.5 -1.2 3.0 
10:30 0.6 -1.5 2.7 
11:OO" 0.6 -1.0 3.0 
11:30 0.5 
-1.2 2.8 
12:OO 0.6 -1.0 2.7 
12:30 0.6 -1.2 3.0 
13~00 0.5 -1.0 3.0 
13:30 0.5 -1.3 3.2 
14:OO 0.5 -1.5 3.1 
14:30 0.5 
-1.3 3.0 
15:OO 0.5 -1.6 2.9 
DMSO-Treatment Data Analysis 
RANGE S.E. 
VARIANCE 
*N=15 observations 
19 
TABLE 2. --Continued. 
TIME MEAN MIN MAX RANGE S.E. VARIANCE 
*N= 15 observations 
TABLE 3.--Statistics for Control and. Treatment HR (bpm) 
~=16 Unless Otherwise 1nd.icated. 
Control Data Analysis 
-- - -- 
TIME MEAN 
0O:OO 146.9 
00:02 147.2 
OO:O4 147.8 
00:06* 148.6 
00:08* 149.0 
0O:lo 147.6 
00:12 147.5 
OO:l4* 146.0 
00:16 148.2 
00:18 147.0 
00:20 147.6 
00:22 147.3 
00:24 147.0 
00:26* 146.2 
00:28 146.0 
00:30 147.2 
OO:32 147.1 
00:34 146.5 
00:36 146.7 
00:38* 149.0 
OO:4O 146.8 
00:42 146.6 
00:44 146.3 
00:46 147.4 
00:48 146.6 
00:50 146.8 
00:52 146.8 
00:54 146.5 
00:56* 144.4 
00:58* 145.5 
0l:OO 146.4 
0l:lO 146.5 
01:20 -146.8 
01:30 146.5 
01:40 146.3 
01:50* 144.8 
MIN MAX 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200 . 0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
200.0 
RANGE 
80.0 
80.0 
80.0 
80.0 
80.0 
80.0 
80.0 
80.0 
82.9 
82.9 
80.0 
82.9 
82.9 
82. 9 
82.9 
82.9 
82.9 
82.9 
82.9 
80.0 
82.9 
80.0 
82.9 
80.0 
80.0 
80.0 
80.0 
80.0 
85.7 
80.0 
80.0 
80.0 
80.0 
80.0 
82.9 
85.7 
82.9 
85.7 
85.7 
85.7 
85.7 
S.E. 
VARIANCE 
*N= 15 observations 
**N=14 observations 
TABLE 3.--Continued 
TIME MEAN MIN MAX RANGE S.E. VARIANCE 
DMSO Treatment Data Analysis 
*N= 15 observations 
**N= 14 observations 
22 
TABLE 3.--Continue
d 
TIME MEAN MIPT MAX RANGE S.E. VARIANCE 
03:oo 152. I 72.7 
03:30 131.7 70.6 
O4:OO 132.1 71.6 
04:30 132.4 70.6 
05:OO 133.8 70.6 
05:30 132.7 70.6 
06:OO 133.1 68.6 
06:30 132.9 68.6 
07:00* 130.7 68.6 
07:30* 131.5 70.6 
08:00* 136.8 70.6 
08:30* 135.0 70.6 
09:OO 135.1 68.6 
09:30 136.4 68.6 
10:00* 155.4 68.6 
10:30* 134.9 68.6 
11:00**140.4 106.7 
- 11:30* 135.7 68.6 
12:00x 134.1 68.6 
12:30 134.6 69.6 
13:OO 135.4 69.6 
13:30 135.2 67.6 
14:OOx 135.8 70.6 
14:3**133.4 70.6 
15:OO 135.0 69.6 
*N= 15 observations 
**&I4 observations 
TABLE 4.--Statistics for Control and. Treatment R Wave (mvs) 
N= 16 Unless Otherwise 1nd.icated. 
Control Data Analysis 
TIME MEAN MIN MAX 
0O:OO 041 0.12 0.85 
00:02 0.41 0.06 0.83 
00:04 0.41 0.11 0.87 
00:06 0.41 0 0.90 
00:08* 0.44 
0.1 1 0.91 
00: 10 0.43 0.14 0.87 
00: 12 0.42 0.12 0.85 
00: 14" 0.39 0.14 0.77 
00: 16 0.42 0.13 0.83 
00:18 0.42 0.07 0.87 
00:20 0.42 0.10 0.85 
00:22 0.42 0.09 0.84 
00:24 0.42 0.15 0.85 
00:26* 0.41 0.11 0.86 
00:28 0.43 0.15 0.85 
00:30 0.41 0.07 0.85 
00:32 0.42 0.15 0.85 
00:34 0.41 0.09 0.85 
00:36 0.42 0.09 0.85 
00:38* 0.44 0.07 0.85 
00:40 0.42 0.12 0.85 
00:42 0.41 0.14 0.85 
00:44 0.41 0.10 0.82 
00:46 0.42 0.09 0.86 
00:48 0.42 0.10 0.85 
00:50 0.42 0.14 0.84 
00:52 0.42 0.11 0.85 
00:54* 0.42 0.09 0.85 
00:56* 0.40 0.12 0.85 
00:58* 0.40 0.12 0.83 
01:OO 0.43 0.14 0.85 
01:10 0.41 0.11 0.82 
01:20 0-42 0,07 0.85 
01:30 0.41 0.12 0.82 
01:40 0.41 0.12 0.85 
01:50* 0.43 0.10 0.84 
02:OO 0.41 0.10 0.85 
02:30 0.42 0.15 0.85 
03:00**0.43 0.14 0.86 
03:30* 0.44 0.14 0.85 
04:OO 0.42 0.12 0.85 
*N= 15 observations 
**N= 14 observations 
RANGE 
0.73 
0.77 
0.76 
0.75 
0.80 
0. 73 
0.73 
0.63 
0.70 
0.80 
0.75 
0.75 
0.70 
0.86 
0.85 
0.78 
0.70 
0.76 
0.76 
0.78 
0.73 
0.71 
0.72 
0.77 
0.75 
0.70 
0.74 
0.76 
0.73 
0.71 
0.71 
0.71 
0.78 
0.70 
0.73 
0. 74 
0.75 
0.70 
0.72 
0.71 
0.73 
S.E. 
0.061 
0.060 
0.065 
0.063 
0.066 
0.062 
0.061 
0.059 
0.062 
0.065 
0.063 
0.063 
0.062 
0.064 
0.063 
0.068 
0.064 
0.064 
0.062 
0.065 
0.063 
0.063 
0.063 
0.064 
0.063 
0.061 
0.061 
0.069 
0.064 
0.065 
0.061 
0.063 
0.066 
0.061 
0.064 
0.066 
0.064 
0.063 
0.071 
0.066 
0.066 
VARIANCE 
24 
TABLE 4. --Continued. 
TIME MEAN MIN MAX RANGE 
04:30* 0.44 0.10 0.87 0.77 
05:OO 0.43 0.09 0.86 0.77 
05:30 0.44 0.14 
0.89 0.75 
06:OO 0.42 0.14 0.90 0.76 
06:30 0.43 0.08 0.87 0.79 
07:OO 0.44 
0.11 0.88 0.77 
07:30 0.44 0.10 
0.91 0.81 
08:OO 0.44 0.07 
0.87 0.80 
08:30 0.43 0.06 
0.90 0.84 
09:OO 0.42 0.11 0.88 0.77 
09:30 
0.44 0.11 0.87 0.76 
10:00* 0.42 0.17 0.86 0.69 
10:30* 0.44 0.11 
0.87 0.76 
DMSO Treatment Data Analysis 
VARIANCE 
0.071 
0.066 
0.066 
0.066 
0.071 
0.066 
0.069 
0.064 
0.066 
0.062 
0.063 
0 052 
0.072 
0.065 
0.063 
0.072 
0.070 
0.065 
0.076 
0.072 
0.075 
0.069 
*N= 15 observations 
**N=14 observations 
TABLE 4.--Continued. 
TIME MEAN 
00:36 0.45 
00:38 0.45 
00:40 0.44 
00:42 0.45 
00:44* 0.40 
00:.46 0.44 
00:48 0.44 
00:50 0.44 
00:52 0.42 
00:54 0.43 
00:56 0.41 
00:58* 0.45 
01:00* 0.42 
01: 10 0.42 
01:20 0.39 
01:30 0.37 
01:40 0.37 
01:50 0.35 
02:OO 0.35 
02:30 0.34 
03:OO 0.34 
03:30* 0.32 
04:OO 0.35 
04:30 0.36 
05:OO 0.36 
05:30 0.36 
06:OO 0.38 
06:3O 0.38 
07:00* 0.38 
07:30* 0.39 
08:00* 0.37 
08:30* 0.39 
09:OO 0.40 
09:30 0.40 
10:00* 0..41 
10:30* 0.41 
MIN MAX 
RANGE 
VARIANCE 
*N= 15 observations 
**N= 14 observations 
TABLE 5.--Statistics for Control and. Treatment T Bave (mvs) 
TJ= 16 Unless Otherwise Indicated. 
Control Data Analysis 
TIME MEAN 
0O:OO 0.19 
00:02 0.19 
00:04 0.21 
00:-06 0.23 
00:08* 0.23 
0O:lO 0.22 
00:12 0.22 
00:14**0.19 
00:16 0.20 
00: 18 0.19 
00:20 0.18 
00:22 0.18 
00:24 0.18 
00:26* 0.18 
00:28 0.18 
00:30 0.18 
00:32 0.19 
00:34 0.18 
00:36 0.18 
MIN 
0.01 
0.01 
0.01 
0.01 
0.01 
0.01 
0.01 
0.00 
0.01 
0.01 
0.01 
0.01 
0.00 
0.01 
0.01 
0.00 
0.00 
0.01 
0.01 
0.01 
0.00 
0.01 
0.01 
0.01 
0.00 
0.00 
0.01 
0.01 
0.01 
0.01 
0.00 
0.01 
0.01 
0.01 
0.01 
0.01 
0.01 
0.00 
0.00 
0.00 
0.01 
MAX RANGE VARIANCE 
*N= 15 observations 
**N= 14 observations 
27 
TABLE 5.--Continued. 
TIME MEAN MIN MAX RANGE 
DMSO-Treatment Data Analysis 
00:04 0.12 0.00 0.32 
OO:O6 0.13 0.00 0.35 
00:08* 0.14 0.00 0.40 
00: 10 0.13 0.01 0.50 
00: 12 0.14 0.01 0.51 
00: 14 0.16 0.00 0.56 
00:16 0.17 0.00 0.60 
00: 18 -.Om 18 0.00 0.62 
00:20 0.22 0.00 0.64 
00:22 0.23 0.00 0.65 
00:24* 0.25 0.00 0.65 
00:26 0.24 0.00 0.65 
00:28* 0.27 0.01 0.70 
00:30 0.24 0.00 0.70 
00:32* 0.22 0.00 0.74 
00:34* 0.26 0.00 0.77 
OO:36 0.23 0.00 Oe75 
*N= 15 observations 
**N=14 observations 
S . E . VARIANCE 
28 
TABLE 5.--Continued. 
TIME MEAN MIN MAX RANGE 
0.75 
VARIANCE 
0.045 
0.059 
0.055 
0.036 
0.056 
0.054 
0.039 
0.037 
0.033 
0.029 
0.028 
0.028 
0.021 
0.019 
0.012 
0.01 1 
0.013 
0.010 
0.008 
0.008 
0.008 
0.007 
0.007 
*N= 15 observations 
**N= 14 observations 
On 
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TABLE 6.--T-Test for Paired. Comparisons: DP 
DPO=DP at Time 0, DPA=Minimum DP, DPB=DP at 15 Minutes 
CONTROL TREATMENT D 
BLOCK DPO - DPA = XI DPO - DPA = 
X2 X2-X1 
1 85 70 15 65 
27 38 23 
2 66 
66 0 5 1 
32 19 19 
3 - 145 137 8 50 2 1 29 21 - 
4 65 60 5 35 18 
17 12 
5 47 45 2 65 27 38 36 
6 55 50 5 43 35 8 3 
7 44 39 5 42 16 
26 18 
11 
8 56 54 2 35 17 16 
9 82 68 14 77 68 9 -5 
10 50 45 5 39 35 30 
11 
65 65 o 60 74 44 16 16 
12 100 78 22 50 37 13 -9 
13 40 30 10 80 
0 
46 
34 80 
36 
14 50 50 100 20 80 
15 46 41 5 6 1 30 3 1 26 
16 8 Lt 83 1 55 15 40 39 
t=Lt. 258** (P<O.OOl) 
BLOCK DPO - DPB = XI DPO - DPB = X2 D -- 
1 85 85 O 65 99 -34 - 34 
2 66 66 O 5 1 57 -6 -6 
3 145 1 40 5 50 70 - 20 -15 - 
4 65 65 o 35 50 -15 -15 
5 47 51 -4 65 
80 -15 -1 1 
6 55 58 -3 43 55 -12 -9 
7 44 45 - 1 42 50 -8 -7 
8 56 56 0 35 82 -47 -47 
9 82 68 14 77 83 -6 - 20 
10 5Q 46 4 74 89 -15 -- -19 - 
11 65 70 -5 60 45 15 20 
12 100 78 22 50 70 - 20 -42 
13 40 30 I0 80 80 0 -10 
14 50 70 - 20 100 75 25 
2 
45 
15 46 44 6 1 69 -8 -10 
16 84 86 -2 55 92 -37 -35 
t=2.390* (0.02(P<0.05) 
- >- 
"Significant 
**Highly significant 
TABLE 7. --T-Test for Paired. Comparisons: SP 
SPO=SP at Time 0, SPA=llinimum SP, SPB=SP at 15 Minutes 
CONTROL TREATMENT D 
BLOCK SPO - SPA = 
1 
SPO - SPA = 
X2 X2-X1 
1 1 20 106 14 122 55 67 53 
2 90 89 1 97 73 24 
3 - 181 10 
23 
171 95 36 59 49 - 
4 98 94 4 6 1 30 31 27 
5 76 74 2 94 45 49 47 
6 92 87 5 83 69 14 
108 
9 
7 115 7 75 38 37 30 
8 9 1 88 3 57 25 32 
11 
29 
9 109 98 1 38 1 26 12 1 
10 89 85 4 loo 64 36 32 
11 
90 90 0 100 79 21 21 
12 
132 43 90 69 2 1 -22 
175 65 13 87 22 116 50 66 
1 
44 
14 85 84 142 45 97 
2 
15 
96 
76 74 93 49 44 42 
16 1 46 143 3 79 22 57 54 
t=4.666** (pt0.001) 
BLOCK SPO - SPB = XI SPO - SPB = X2 D -- 
**Highly significant 
TABLE 8.--T-Test for Paired Comparisons: PP 
PPO=PPat Time 0, PPA=Minimwn PP, PPB=PP at 15 Minutes 
CONTROL TREATMENT D 
BLOCK PPO - PPA = 
X1 
PPO - PPA = X2 
X2-X1 
1 35 27 8 57 25 32 24 
2 24 20 4 46 40 6 2 
3. 36 
34 2 45 15 
30 28 
4 33 30 3 11 15 12 - 
26 13 
5 29 28 1 29 16 15 
6 37 32 5 40 34 6 1 
7 7 1 68 3 33 
11 22 19 
8 35 31 4 22 
8 14 10 
9 27 22 5 6 1 46 15 10 
BLOCK PPO - PPB = XI PP0 - PPB = 
X2 
D 
- - 
1 35 33 2 57 67 -10 -12 
2 24 23 I 46 64 -18 -17 
3 36 37 - I 45 45 o 1 
4 33 34 - 1 26 26 0 1 - 
5 29 34 -5 29 30 - 1 
0 
4 
6 37 37 40 48 -8 -8 
7 7 1 75 -4 33 40 -7 -3 
8 35 40 -5 22 28 -6 - 1 
9 27 30 -3 6 1 6 1 O 3 
10 39 40 - 1 26 30 -4 -- -3 - 
11 25 24 1 40 42 -2 -3 
12 75 57 18 40 38 2 -16 
13 47 36 11 36 35 1 -10 
14 35 36 - 1 42 37 5 6 
15 30 3 1 - 1 32 36 -4 -3 
16 62 64 -2 24 19 5 7 
--- 
**Highly significant 
37 
TABLE 9. --T-Test for Paired Comparisons: MAP 
MAPO=MAP at Time 0, MAPA=Minimum MAP, MRPB=MAP at 15 minutes 
CONTROL TREATMENT D 
BLOCK MAP0 - MAPA = XI MAP0 - MATA = 
X2 X2-X1 
1 96.7 82.0 14.7 84.0 37.0 
47.0 32.3 
2 74.0 73.7 0.3 66.3 45.7 20.6 200 3 
3 157.0 148.3 8.7 65.0 26.0 39.0 30.3 
4 - 76.0 71.3 4.7 43.7 22.0 21.7 17.0 
5 56.7 54.7 2.0 74.7 33.0 41.7 39.7 
6 67.3 62.3 5.0 56.3 46.3 10.0 5.0 
7 67.7 62.0 5.7 53.0 30.0 23.0 17.3 
8 67.7 66.3 1.4 
42.3 19.7 
22.6 21.2 
9 91.0 78.0 13.0 97.3 87.3 10.0 -3.0 
10 63.0 58.3 4.7 82.7 
47.3 35.4 30.7 
11 73.3 73.3 0.0 73.3 55.7 17.6 17.6 
12 125.0 96.7 28.3 63.3 47.7 15.6 -12.7 
13 55.7 41.7 14.0 92.0 393 52.7 38.7 
14 61.7 6 0.4 114.0 28.3 85.7 
85.3 
15 56.0 52.0 4.0 
71.7 36.3 35.4 31 04 
16 104.7 103.0 1.7 63.0 
17.3 45.7 44.0 
t=4.684** (P<O.OOl) 
BLOCK MAP0 - MAPB = XI MAP0 - MAPB = 
X2 D 
"Significant 
**Highly Significant 
TABLE 10. --T-Test for Paired. Comparisons: CVP 
CVPO=CVP at Time 0, CVPA=Maximum CVP, CVPB=CVP at 15 Minutes 
CONTROL TREATMENT D 
BLOCK CVPO - CVPA = X1 CVPO - CVPA = X2 X2-X1 
BLOCK CVPO - CVPB = XI CVPO - CVPB = X2 D 
- - 
-- - - 
- -- 
**Highly significant 
39 
TABLE 1 1. --T-Test for Paired. Comparisons: HR 
HRO=HR at Time 0, HRAzMinirnum HR, HRB=HR at 15 Minutes 
CONTROL TREATMENT D 
BLOCK HRO - HRA = XI HRO - HRA = 
X2 X2-X1 
1 166.7 148.1 18.6 75.0 61.5 13.5 -5.1 
2 150.0 141.2 
8.8 165.5 121.2 44.3 35.5 
3 150.0 150.0 0.0 145.4 98.0 47.4 47.4 
4 - 120.0 100eO 20.0 117.1 106.7 10.4 -9 e6 
5 123.1 111.6 11.5 171.4 145.4 26.0 14.5 
6 120.0 117.1 
2.9 1 106.7 26.6 23.7 
7 150.0 150.0 0.0 141.2 120.0 
21.2 21.2 
8 171.4 154.8 6.6 154.8 120.0 34.8 18.2 
9 129.8 120.0 9.8 200.0 177.8 22.2 12.4 
10 165.5 160.0 5.5 133.3 120.0 13.3 
7.8 
11 133.3 117.1 16.2 150.0 150.0 0.0 -16.2 
12 200.0 200.0 0.0 
133e.3 126.3 7.0 7.0 
13 129.7 121.2 8.5 192.0 171.4 20.6 12.1 
14 120.0 117.1 2.9 160.0 51.1 108.9 106.0 
15 154.8 150.0 4.8 133.3 104.3 29.0 24.2 
16 165.5 160.0 5.5 
133.3 72.7 60.6 55.1 
t=3.023** (0.005<P<Oe0 1 ) 
- - - - -- - 
BLOCK HRO - HRB = 
X1 
HRO - HRB = X2 D 
- - 
- -- 
**Highly significant 
TABLE 12.--T-Test for Paired Comparisons: R Magnitude 
RO=R at Time 0, RkMaximum R, RB=R at 15 Minutes 
CONTROL TREATMENT D 
BLOCK RO - RA = X 
1 
RO - RA = X2 X2-XI 
1 0.40 0.40 0.00 0.1 0.43 -0.27 -0.27 
2 0.19 0.28 -0.09 0.5; 0.92 -0.35 -0.26 
3 0.52 0.61 -0.09 0.63 1.25 -0.62 -0.53 
4 - 0.3 0.19 -0.06 0.54 0.06 -0.06 0.00- 
5 0.73 0.92 -0.19 0.28 0.43 -0.15 0.04 
6 0.25 0.32 -0.07 0.49 0.51 -0.02 0.05 
7 0.75 0.80 -0.05 0.56 0.66 -0.10 -0.05 
8 0.64 0.91 -0.27 0.03 0.42 -0.39 -0.12 
9 0.24 0.26 -0.01 0.36 0.66 -0.30 -0.29 
10 0.85 0.91 -0.06 0.37 0.65 -0.28 -0.22 
11 0.30 0.33 -0.03 0.63 0.76 -0.13 -0.10 
12 0.14 0.16 -0.02 0.41 0.56 -0.15 -0.13 
13 0.42 0.43 -0.01 
O.IO 0. I9 -0.09 -0.08 
14 2 0.26 -0.14 
0.06 0.11 -0.05 0.09 
15 0.29 0.33 -0.04 1.05 1.06 -0.01 0.03 
16 Oa61 0.63 -0.02 
0.25 0.31 -0.06 -0204 
t=2.886* (0.01<~<0.02) 
--- 
BLOCK RO - RB = X
I 
RO - RB = 
X2 D - - 
1 0.40 0.31 0.09 0.16 0.18 -0.02 -0.1 1 
2 
- 0.19 0.26 -0.07 0.57 0.47 0.10 0.17 
3 0.52 0.47 0.05 0.63 
0.67 -0.04 -0.09 
4 0.13 0.19 -0.06 0.54 
0.51 0.03 0.09 - 
5 0.73 0.92 -0.19 0.28 0.43 -0.15 0.04 
6 0.25 0.27 -0.02 0.49 0.49 0.00 
0.02 
7 0.75 0.65 0.10 0.56 
0.56 0.00 -0.10 
8 0.64 0.86 -0.22 0.03 0.07 -0.04 0.18 
9 0.24 0.26 -0.02 0.36 0.33 0.03 0.05 
I0 0.85 0.85 0.00 0.37 0.40 -0.03 -0.03 
11 0.30 0.31 -0.01 0.63 0.42 0.21 -- 0.22- 
12 0.14 0.12 0.02 0.41 0.40 0.01 -0.01 
13 0.42 0.43 
-0.01 0.10 Oal9 -0.09 -0.08 
14 0.12 0.15 -0.03 0.06 
0.05 0.01 0.04 
15 0.29 0.33 -0.04 
1.05 0.98 0.07 0.11 
16 0.61 0.60 0.01 0.25 0.22 
0.03 0.02 
t=1.269 (0.20<P<0.50) 
Mean Arterial Pressure 
The mean DMSO-treatment MAP, after a short initial 
rise (Figure 1) of approximately 6 seconds after the 
beginning of injection, plummeted. until it reached a 
mean minimum at 30.3 seconds. The difference in MAP 
between treated and control animals was highly significant 
(P(0.001). From this minimum value the MAP gradually 
increased. After approximately 3 1/2 minutes it regained 
the original MAP value record.ed. at time 0, and, continued. 
to rise until it reached. a maximum at approximately 9 
minutes. At the end of the experiment the MU was still 
significantly different from the control (0.01<P<0.02). 
The control MAP remained fairly constant throughout the 
15 minutes except for a brief increase of approximately -- 
10 second.~ immed.iately after the beginning of the saline 
injection. - 
Central Venous Pressure 
Figure 2 illustrates the mean (+S.E.) - CVP values 
-- 
for both control and treatment animals. After DMSO 
injection, the CVP rose rapidly, reached a mean maximum 
at 1 minute 40 seconds, then slowly declined, although 
still remaining far above the initial value by the end 
of the experiments. Differences in CVP for treatment 
and control animals vere highly significant (P(0.00 1 ) 
at both t and tb. The control CVP demonstrated, a short 
a 
initial rise, then remained. near the time 0 value for the 
remaind.er of the experiment. 
Heart Rate 
The mean HR (-I-S.E.) - is plotted. in Figure 3. The 
control and treatment values were initially very similar. 
The control remained basically constant, with a slight 
decrease t0ward.s the end of the experiment, HR of DMSO- 
treated. animals, however, quickly d.ropped. to a mean min- 
imum at 28  second.^, a value significant in its d.ifference 
from the control. The rate then sloivly increased. until, 
at the end. of the experiment, there was no longer any 
significant d.if ference between the control and experimental 
- - 
values at the 5% level. 
R :!lave Magnitude - 
The control and. DMSO R values were also initially 
similar, as seen in Figure 4 and Table 4. The control 
increased slightly towards the end of the 15 minutFs, but 
DMSO R values were significantly elevated (0.0 1(P<0.02) 
over the control during the initial 30 seconds. The 
amplitude of the R wave then gradually decreased, reaching 
,- minimum at 2 minutes 30 seconds. By the end of the 
- -- 
experiment, there ~as no longer a significant difference 
at the 5% level between the control and DMSO R values, 
Figure 5 illustrates the T wave pattern over the 
course of the experiments. Since the T deflection could 
normally be either positive or negative, the absolute 
value of T was plotted and used for calculations. The 
control T exhibited. an initial rapid increase d.uring the 
first 8  second.^, then returned. to near initial values for 
the remaind.er of the time. The DNSO T values became 
significantly elevated. (0.0 1 lP<0.02) soon after injection; 
the graph peaks at 28  second.^. The T amp1itud.e then 
dropped. below the initial recording at time 0, but by the 
end, of the experiments, on the average, there was no longer 
a-ny significant difference (P)0.05) between the control 
and experimental values. - - 
Thirteen of the 16 control T wave recordings were 
positive and. 3 were negative. The d.irection of the de- - 
flection remained the same throughout the experiment. For 
the DIG0 trials, hoaever, only six experiments mere con- 
sistantly positive and. four consistantly negative. Of 
-- 
these, two had. S-T segment elevations beginning approx- 
imately 10 seconds after injection of DMSO began. A 
third demonstrated, a depressed. S-T segment at the 10 
second. time nhich became quite marked. by 28 seconds. By 
six minutes, the S-T segment had returned to normal. The- _ 
remaining six DMSO trials demonstrated reversals in the 
direction of the T vave deflection and snitched betaeen 
t 
monophasic and diphasic waves. These reversals occur,ed 
several times in the course of each experiment, usually 
beginning 10 to 30 seconds after the initiation of the 
DMSO injection. 
Pearson Correlation 
Data from the DMSO-treatment MAP trials were 
subjected to a simple linear correlation analysis 
(Pearson Correlation Coefficient). These data, the cor- 
relation coefficients, and two-tailed probability values 
are presented in Table 14. The means and standard de-- 
viathons of the variables examined were also evaluated: 
MAP(X1)=32.7 (+ - 19.549) mrflHg - - 
MW(X2)=13.7 b-18.292) - mmHg 
Time Az30.3 (+ 1 1.287) seconds 
- 
- 
Volume idjected=3.5 (+0.905) ml 
- 
Injection time= 1 1.7 (+6.722) seconds 
- 
\:!eight=3.45 (+0.901) kgs 
- 
The !fAP(xl) is the difference betvieen the t';me 0 
and minimum MAPS, and the MAP(X2) is the difference between 
time 0 MAP and, the M,W at 15 minutes. Time A is the time 
necessary to attain the minimum MAP value after injection 
begins. 
- - 
A significant correlation (P(0.05) was found 
between the minimum MAP and the volume of DMSO injected, 
as well as with the weight of the animal. The time to 
attain minimum MAP was significantly correlated with the 
injection time and. the value of MAP(X,), and the relation- 
ship to weight was highly significant (P<0.01). No 
significant correlation existed. between MA.P(X1)  and^ the 
injection time, nor between MPP(X2) and any of the variables 
tested.. 
TABLE 14. --Pearson Correlation N= 16 
MAP(X1)=MAP at Time 0 - Minimum MAP 
MAP(X )=MAP at Time 0 - MAP at 15 Minutes 
Time $=~ime to Reach Minimum MAP 
MJQ(X1 VOLUME INJECTION 
INJECTED iS1SEIGHT TIME MAP( X2) 
COEFFICIENT 0.5841 0.588 1 0.2122 -0.2922 
SIGNIFICANCE 0.018* 
0,0l7* 0.430 0.272 
VOLUME INJECTION 
INJECTED ':EIGHT TIME MmXI ) 
COEFFICIENT -0.1182 -0.1053 -0.1107 -0.2922 
SIGNIFICANCE 0.663 0.698 0.683 
0.272 
TIME A INJECTION 
TIME !'IEI GHT Mm(X1) MUJ(X2) -- 
COEFFICIENT 0.5410 0.6494 0.5525 0.2523 
SIGNIFICANCE 0.029" 0.006** 0.026* 0. 346 
*Significant 
**Highly significant 
DISCUSSION 
From the results, dramatic effects on the cardio- 
vascular system asre evident after injection of DP4SO. 
Hoaever, the mechanisms behind these results are not always 
clear. 
The transient increase in MAP during the first few 
seconds of the experiments is most likely simply the re- 
sponse to the blood volume change as the injection is intro- 
duced.. The increase is evid.ent in both the experimental 
and. the control trials. 
After this initial increase, the IlnP elicits a dj-- 
phasic response in the DMSO experiments. Falling quickly 
d.uring the first then gradually increases 
md is significantly elevated by the end of the experi- 
- - 
ment. Only tao sources are respon-sible for a change in 
MAP: (1) the volume of blood. distending the arteries, or 
- 
card.iac output (C.O,), and. (2) the resistance offered by 
the peripheral circulatory system, or total peripheral 
resistance (TPR). Increasing either value v~ill increase 
the I4U. 
-- 
The C.O., in turn, is determined by I-IR and SV: 
(C,O.=WR x SV). Evidence for a change in HR is available 
directly from the ECG tracings, and the change corresponds 
very closely vith the fluctuations in MAP during the first 
- -- 
few minutes of the experiments. The PTL? and HR simultane- 
ously decrease, then gradually increase, Hoaever, the HR does 
not follow the eventual elevation seen in the MAP, but re- 
mains near normal values. That is causing the changes in 
IIR? 
Evidence for a direct effect on the heart by DMSO 
is gathered by interpretation of the ECG tracings. The - 
R and T waves become elevated during the first minute, 
then return to near normal values. This response is 
perhaps reflective of electrophysiological or permeability 
changes within the cells of the heart itself. According 
to Bolton ( 1975), bradycardia and T wave amplification 
occur with hyperkalemia. Although its effects are not 
well established, hypercalcemia is also believed to result 
in increased T wave magnitude, as sell as S-T segment 
elevation. David et ale (1982) found that persistent 
- - 
increases in the R wave amplitude occurred in association 
aith z marked delay in intramyocardial conduction. Accord- 
- 
ing to Hill and Gettes (1980), higher interstitial potassium 
concentrations could cause this delay. 
Myocardial hypoxia is also a possible cause of 
the ECG fluctuations. It may be signalled. by changes 
in the magnitud.e or d.irection of deflection of the T wave, 
and. S-T segment elevation or depression. All of these 
phenomena were noted in various DTvISO trials, but never 
-~ 
in the controls. The hypoxia may be d.ue to a decreased 
- - 
respiratory rate or perhaps a d.ecreased. blood supply to the 
heart. due to the decreased MAP. DiStefano ( 1965) noted 
apnea in his experiments with cats, and reported artificial 
respiration vas often needed after the Df4SO injection. 
That extreme aas never needed in this research, however a 
depressed respiratory rate was occasionally noted immedi- 
ately after the injection. 
Stroke volume increases if there is an increase in 
the fiber length of the cardiac muscle (Starling's La171 
of the Heart), as aould occur with increased ventricular 
filling. The CVP measured at the entrance of the 
right atrium, and its increased pressure could be reflective 
d 
of increased venous return. In obwance to Starling's Lac, 
as more blood fills the ventricles a greater force of 
contraction results and, consequently, a greater volumc - - 
of blood is ejected. The stroke volume increase could 
also be augmented by the decreased HR, which permits 
- 
more time for ventricular filling. 
In addition, Shlafer (1975) theorized that osmotic 
stress imposed on the myocardial cell could produce 
-. . 
positive inotropy. He suggested that the cell undergoes - 
dehydration upon exposure to DMSO, which would tend to 
raise the apparent intracellular concentration of free 
++ 
solutes, most notably ~a++. This Ca is then available 
to activate the myofibrils and., therefore, increase the 
force of contraction. 
The increased venous return could result from an 
increased plasma volume. Klingman (1965) presented 
evidence that topica.11~ applied DYSO ca-uses histamine 
release, resulting in peripheral vasodilation and increased 
vascular leakage. '',%en the MAP decreases, the filtration 
pressure in the capillaries also decreases, and fluid could 
floe into the circulatory system from surrounding tissues, 
The central nervous system could also be affecting the 
venous return. Yhen the MJn9 decreases, baroreceptors 
detect the pressure difference and the sympathetic nervous 
system is strongly stimulated within a fey! seconds. The 
effects of this stimulation are manifested by (1) increa.sed 
tone of most of the blood vessels in the circulatory 
system, especially the veins, and (2) stimulation of 
- - 
the heart to increase the force of contraction. There 
is therefore an increased tendency for blood to flow 
- 
back to the heart, further increasing the CVP. 
Another mechanism affecting the MAP is the TPR. 
This variable was not d.irectly measured., and. is influenced. 
-- 
primarily by the diameter of the arterioles. Vasocon- 
striction may be occuf ng, further increasing the MAP and 
counteracting the vasodilating effect of the histamine, 
but this is unknonn. 
The results of the Pearson Correlation analyses 
.are not alnays explicable from the data obtained in this 
research, nor aere the relationships tested even mentioned 
in the available literature. '.'lhy, for exanzple, does the 
magnitude of the maximum MAP response increase vnth an 
increase in the veight of the animal and the amount of 
DFISO injected, if the dosage mas kept constant? One pos- 
sible explanation is the fact that larger animals tend t~ 
have a lower metabolic rate, thus they nould tend to break 
domt the drug at a reduced rate and more ~~~ould be available 
for a longer period of time to affect the body. 
It is logical, however, that the time to reach this 
maximum response increases as the aeight of the animal 
increases because it usually took longer to inject the 
larger volume of drug. But why is there also a signifi- 
cant correlation betvreen the time to reach the maximum 
- - 
effect and the magnitude of the effect? 
Further research is necessary to answer these ques- 
- 
tions. Determining more specifically the role of the 
central nervous system in relation to its effect on the 
heart, blood vessel constriction and respiration after 
DFtSO administration nould provide valuable information, as 
~rould further investigation of the nature of cell perm- 
eability changes. 
In summary, DPISO administration exhibits rather 
remarkable effects on just about every parameter of the 
- 
cardiovascular system, not all of vhich are easily 
- 
explained. Possibly because of a direct effect on the 
cells of the heart itself, DMSO causes the classic symptoms 
of acute heart failure: a reduced heart rate and con- 
com_itant drop in MAP. As the body compensates with 
increased SV and a gradually increasing HR, the MAP 
returns to normal, then becomes significantly elevated, 
possibly due to positive inotropy. This research 
answered a fern questions and raised many more. The known 
factors as well as the unknorrn possibilities should be 
taken into consid.eration before clinical administration 
of the d.rug. 
APPENDIX 
Control and. DMSO-Treatment Data 
The appendix lists the data obtained from control 
(+#I-$16) and DMSO-treatment (#I?-#32) animals. The 
sex, weight, total injection time (beginning at time 0), 
and the volume injected are given for each trial. 
Time (minutes:seconds), diastolic, systolic, pulse, 
mean arterial and central venous pressures (rnmHg) , 
HR (bpm), R and T wave magnitudes (mvs) are recorded 
for each of 63 time periods per trial over a 15 minute 
interval. 
- - 
55 
APPENDIX 
Control Data 
1. Female Weight=5.03 kg Injection Time=20.0 secs 
Amount Injecte,&5.0 ml 
TIME- 
00 : 00 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00: 24 
00 : 26 
00:28 
00:30 
00:32 
00:34 
00: 36 
00 : 38 
00: 40 
00 : 42 
00:44 
00 : 46 
00 : 48 
00:50 
00: 52 
MAP CVP 
0.4 
0.4 
0.6 
0.7 
0.7 
0.7 
0.7 
0.7 
0.7 
0.7 
0.9 
0.9 
0.9 
0.7 
0.7 
0.9 
0.7 
0.6 
0.7 
0.4 
0.7 
0.1 
0.4 
0.1 
0.6 
0.4 
0.6 
0.1 
0.7 
0.3 
0.6 
0.3 
0.7 
Oa4 
0.4 
0.2 
0.0 
-0.3 
-0.3 
-0.6 
56 
APPENDIX (Continued) 
-- - 
TIME DP SP PP 
1.04:OO 90 132 42 
04:30 81 123 42 
05:OO 77 115 38 
05:30 77 113 36 
06:W 75 110 35 
06:30 73 108 35 
07:OO 70 108 38 
07:30 70 106 36 
08:OO 74 109 35 
08:30 77 112 35 
O9:OO 82 115 33 
O9:3O 82 116 34 
10:OO 82 116 34 
MAP CVP 
104oO -0.4 
95.0 0.6 
89.7 -0.6 
89.0 -0.4 
86.7 0.3 
84.7 -0.3 
82.7 0.0 
82.0 0.0 
85.7 -0.3 
88.7 -0.7 
93.0 -0.9 
93.3 -0.6 
93.3 -1.2 
91.7 -1.5 
92.0 -0.9 
94.0 -0.9 
91.7 -0.9 
93.3 -0.7 
93.0 -1.0 
92.7 -1.3 
93.3 -1.2 
96.0 -1.3 
96.0 -1.6 
2. Female Weight=&. 67 kg Injection Time= 10.5 secs 
Amount In jected=4.7 ml 
- 
0O:OO 66 90 24 74.0 0.7 150.0 
0.19 0.02 
OO:O2 68 93 25 76.3 0.7 150.0 
0.24 0.02 
00:04 68 93 25 76.3 0.8 150.0 
0.19 0.02 
00:06 70 94 24 78.0 1.0 
150.0 0.22 0.03 
00:08 68 94 26 76.6 1.2 150.0 0.16 
0.03 
00:lO 70 95 25 78.3 1.5 150.0 
0.17 0.02 
00: 12 -69 95 26 77.7 
1.0 150.0 0.22 
--0.04 - 
00:14 67 92 25 75.3 1.0 
150.0 0.18 0.03 
00: 16 67 94 27 76.0 1.0 
150.0 0.22 0.04 
00:18 66 91 25 74.3 1.0 150.0 0.20 0.03 
00:20 67 93 26 75.7 1.2 
150.0 0.22 0.02 
OO:22 68 93 25 76.3 1.0 150.0 0.23 0.03 
00:24 69 93 24 77.0 1.2 
150.0 0.20 0.02 
00:26 70 95 25 78.3 1.0 
150.0 0.22 0.02 
00:28 70 95 25 78.3 1.2 
150.0 0.20 0.02 - 
00:30 70 95 25 78.3 1.2 150.0 0.20 0.02 
00:32 70 94 24 78.0 1.0 150.0 0.21 0.02 - - 
00~34 70 94 24 78.0 1.2 150eO 0.19 0.02 
00:36 70 95 25 78.3 1.1 150.0 0.24 0.02 
APPENDIX ( Continued) 
TIME MAP 
v 
78e3 
78e3 
78-0 
78e3 
78.0 
78.3 
78e3 
78,O 
78e3 
78,O 
78.3 
78e3 
77.0 
75.3 
76.7 
77.3 
78eO 
77.0 
77.3 
77eO 
77.0 
77.0 
76.7 
77.7 
77e7 
78e3 
78e3 
79.0 
79eO 
78.3 
79eO 
79.7 
82e3 
81e7 
80.0 
79.0 
77.3 
75.3 
73.7 
75.3 
75.3 
74.7 
73.7 
CVP 
- 
1.2 
1*2 
1.2 
1.1 
1e2 
1.0 
1e2 
1 eo 
1.2 
1e2 
1 eo 
1e2 
1e2 
1e2 
1e2 
1 eo 
1 eo 
1 eo 
0.8 
1 eo 
0*7 
o* 7 
0.9 
oe7 
0.8 
1 eo 
1 eo 
1.0 
Oe 7 
Oe7 
0.7 
0.7 
0.5 
Oe6 
1 eo 
Oe7 
0*7 
0.7 
0.7 
oe5 
1.0 
1.0 
1 eo 
1 eo 
APPENDIX ( Continued) 
3. Female Weighb3.96 kg Injection Time= 19.0 secs 
Amount Injected=4.0 rnl 
TIME MAP CVP 
0,7 
0.9 
1 a0 
1 eo 
1 .o 
1 .o 
1.1 
1.1 
1 .o 
1.1 
1 eo 
1 eo 
1.0 
0.9 
1 eo 
1 eo 
1 .o 
1 eo 
1 eo 
1 a0 
1 eo 
1 eo 
1 eo 
1 eo 
1 eo 
1 .o 
1 a0 
1 eo 
1 eo 
1 .o 
1 a0 
1 eo 
1 eo 
1 eo 
1 a0 
1 eo 
1 eo 
1 .o 
1 eo 
0.6 
1 eo 
1 eo 
APPENDIX ( Continued) 
TIME DP SP PP MAP CVP HR R T 
3. 05:OO 137 171 34 148.3 1.0 150.0 0.55 0.25 
05:30 137 171 34 148.3 1.0 150.0 0.55 0.24 
06:OO 137 172 35 148.7 1.0 150.0 0.53 0.24 
O6:3O 137 171 34 148.3 1.0 150.0 0.55 0.24 
07:OO 137 172 35 148.7 . 0.7 150.0 0.51 0.25 
07:30 138 174 36 150*0 0.9 150.0 0.55 0.24 
08:OO 140 175 35 151.7 1.0 15OeO 0.50 0.23 
08~30 139 174 35 150.7 1.0 150.0 0.52 0.25 
09:oo 141 175 34 152.3 1.0 150.0 0.51 0.20 
09:30 140 175 35 151.7 1.2 150.0 0.50 0.24 
1O:OO 139 175 36 151.0 1.1 150.0 0.50 0.25 
10~30 141 176 35 152.7 1.1 150.0 
0.50 0.21 
1I:OO 141 177 36 153.0 1.2 150.0 
0.50 0.21 
11:30 140 177 37 152.3 1.2 150.0 0.50 0.22 
12~00 141 177 36 153.0 1.2 150.0 0.50 0.20 
12:30 140 176 36 152.0 1.2 150.0 
0.50 0.20 
13:oo 141 177 36 153.0 1.2 15OoO 
0.49 0.20 
13:30 141 177 36 
153.0 1.2 150.0 
0.51 0.20 
14:OO 140 176 36 152.0 1.5 150.0 0.49 0.20 
14:30 141 179 38 
153.7 1.2 150.0 
0.51 0.20 
15:OO 140 177 37 152.3 1.7 150.0 
0.47 0.20 
- - 
4. Female Weight=3.46 kg Injection Timez5.5 secs 
Amount Injected=3.5 ml 
APPENDIX (Continued) 
TIME DP SP PP MAP CVP HR R T 
4. 00:40 65 99 34 76.3 2.2 117.1 0.17 0.02 
00:42 65 99 34 76.3 2.5 120.0 0.14 0.01 
00:44 65 99 34 76.3 2.4 120.0 
0.16 0.02 
00:46 64 98 34 75.3 2.2 120.0 0.17 0.02- 
00:48 64 98 34 75.3 2.2 120.0 0.14 0.02 
00:50 64 98 34 75.3 2.2 120.0 0.14 0.03 
00:52 64 98 34 75.3 2.2 120.0 0.16 0.03 
00:54 64 98 34 75.3 2.2 120.0 0.17 0.03 
0036 64 98 34 75.3 2.1 114.3 0.16 0.03 
00:58 64 98 34 75,3 2.1 120.0 0.17 0.03 
Oil:0O 64 97 33 75.0 2.2 120.0 0.17 0.01 
0l:lO 64 99 35 75.7 2.5 120.0 0.14 0.02 
01:20 64 97 33 75.0 2.5 120.0 0.14 0.04 
Ol:30 63 97 34 74.3 2.5 120.0 0.13 0.02 
01:40 63 97 34 74.3 2.2 117.1 0.14 0.02 
01:50 62 96 
34 73.3 2.2 114.3 0.16 0.03 
02:OO 63 97 34 74.3 2.2 117.1 0.14 0.04 
02:30 61 95 
34 72.3 2.0 114.3 0.16 0.03 
03:OO 61 
95 34 72.3 2.0 114.3 0.14 0.03 
03:30 61 95 34 72.3 2.0 114.3 0.14 0.04 
04:OO 61 95 
34 72.3 1.7 114.3 0.13 0.05 
04:30 61 95 34 72.3 1.7 109.1 0.17 0.04 -- 
0200 61 95 34 
72.3 1.5 109.1 0.16 0.04 
05:30 61 95 34 72.3 1.5 109';l' 0.16 0.05 
06:OO 60 94 
34 71.3 1.6 111.6 0.14 0.05 
06:30 60 94 
34 71.3 1.2 109.1 0.16 0.07 - 
07:OO 60 94 
34 71.3 1.2 109.1 0.15 0.14 
OR30 60 94 34 71.3 1.2 109.1 0.16 0.07 
08:OO 60 94 
34 71.3 1.2 109.1 0.16 0.06 
08:30 61 95 34 72.3 1.0 109.1 0.17 0.07 
09:OO 60 
94 34 71.3 1.0 106.7 0.15 0.07 
0930 62 95 33 73.0 1.1 106.7 0.14 0.11 
10:OO 62 
95 33 73.0 2.0 1Q9.1 0.17 -0.06 - 
10:30 63 96 33 74.0 1.0 106.7 0.16 0.08 
11:OO 64 96 32 74.7 1.0 104.3 0.16 0.06 
11:30 64 96 32 74.7 1.0 104.3 0.17 0.06 
1200 64 96 32 74.7 0.9 100.0 0.16 0.06 
12:X 64 95 32 74.3 0.9 102.1 0.19 0.06 
13:00 64 96 32 74.7 0.7 102.1 0.17 0.06 
13: 65 95 30 75.0 0.6 100.0 0.17 0.09 
14:OO 65 98 33 76.0 0.7 100.0 0.18 0.09 - 
14:30 65 96 31 75.3 0.6 102.1 0.19 0.07 
15:OO 65 99 34 
76.3 0.5 100.0 0.19 0.09 
- 
APPENDIX (Continued.) 
5. Female Weight=3,06 kg Injection Time=8.0 secs 
Amount Injecte&3.1 rnl 
TIME 
00 : 00 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00:22 
00:24 
00: 26 
00: 28 
00 : 30 
00 : 32 
00 : 34 
00 : 36 
00 : 38 
00 : 40 
00:42 
00: 44 
00:46 
00 : 48 
00 : 50 
00: 52 
MAP CVP 
APPENDIX ( Continued) 
TIME DP SP PP MAP CVP HR R T 
6. Female Weightm3.03 kg Injection Time=l 1.0 secs -- 
Amount Injected=3.0 ml 
63 
APPENDIX ( Continued.) 
- 
TIME DP SP PP MAP CVP HR R T 
APPENDIX ( Continued) 
7. Female Weighk2.99 kg Injection Time=4.0 secs 
Amount Injected=3.0 ml 
TIME 
0O:DO 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00 : 20 
00: 22 
00: 24 
00: 26 
00: 28 
00: 30 
MAP CVP 
APPENDIX (Continued) 
TIME DP SP PP MAP CVP HR R T 
7. 05:OO 41 114 73 65.3 0.8 150.0 0.70 0.15 
05:30 41 111 70 64.3 
1.0 150.0 0.70 0.13 
06:OO 41 113 72 65.0 1.0 150.0 0.70 
0.15 
06:30 41 111 70 64.3 1.0 150.0 
0.70 0.15 
07:OO 41 110 69 64.0 1.5 150.0 0.72 
0.15 
07:30 44 114 70 
67.3 - 154.8 0.70 0.15 
08:OO 41 111 70 64.3 2.0 150.0 0.70 0.15 
08:30 42 112 70 65.3 1.7 150.0 0.72 0.15 
09:OO 44 115 71 67.7 1.5 150.0 0.70 
0.15 
09:30 44 115 71 67.7 1.2 150;O 
0.72 0.15 
1O:OO 44 118 74 68.7 1.5 150.0 0.67 0.13 
lO:3O 45 120 75 70.0 1.6 150.0 0.67 
0.14 
11:OO 45 120 75 70.0 1.2 154.8 0.65 0.14 
11:30 45 117 72 69.0 1.0 154.8 0.70 
0.15 
12:OO 45 118 73 69.3 1.1 154.8 0.70 0.15 
12:30 45 120 75 70.0 1.0 154.8 0.65 0.13 
13:OO 45 120 75 70.0 1.0 154.8 0.65 0.14 
13:30 45 120 75 70.0 
1.2 160.0 0.70 0.15 
14:OO 45 120 75 70.0 1.1 150.0 0.61 0.13 
14:30 45 121 76 70.3 1.2 
154.8 0.65 0.15 
15:OO 45 120 75 70.0 1.2 154.8 0.65 0.15 
- - 
8. Female Weight~2.87 kg Injection Time=9.0 secs 
Amount Injected=2.9 ml 
APPENDIX ( Continued.) 
-- --- 
TIME DP SP PP MAP CVP 
HR R T 
APPENDIX (Continued.) 
9. Female Weight=2.79 kg Injection Time=8.5 secs 
Amount Injected=2.8 ml 
TIME 
00 : 00 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00: 24 
00: 26 
00: 28 
MAP CVP 
APPENDIX ( Continued) 
TIME DP SP PP MAP CVP HR R T 
9. 05:OO 81 107 26 89.7 -1.2 123.1 0.22 -0.06 
05:30 80 106 26 88.7 -1.2 123.1 0.23 -0.06 
06:OO 80 107 27 89.0 -1.5 123.1 0.24 -0.06 
O6:3O 80 106 26 88.7 -1.0 123.1 0.20 -0.06 
07:OO 79 105 26 87.7 -1.5 123.1 0.24 -0.06 
07:30 80 108 2% 89.3 -1.7 120.0 0.24 -0.06 
08:OO 79 106 27 88.0 -1.5 123.1 0.25 -0.05 
08:30 80 105 25 88.3 -1.0 120.0 0.23 -0.06 
09:oo 82 104 22 89.3 -1.5 120.0 0.25 -0.06 
09:30 82 104 22 89.3 -0.7 120.0 0.25 -0.06 
1O:OO 76 105 29 85.7 -1.0 123.1 0.26 -0.07 
10:30 76 103 27 85.0 -1.0 120.0 0.26 -0.06 
11:OO 75 103 28 84.3 -1.0 120.0 0.26 -0.06 
11:30 75 103 28 84.3 -1.2 120.0 0.26 -0.06 
12:OO 75 103 28 84.3 -1.0 120.0 0.25 -0.06 
12:30 71 100 29 80.7 -1.2 123.1 0.26 -0.04 
13:OO 73 102 29 82.7 -0.7 123.1 0.22 -0.06 
13:30 69 99 30 79.0 -1.2 - - - 
14:OO 69 99 30 79.0 -1.5 123.1 0.26 -0.06 
14:30 70 100 30 80.0 -1.0 123.1 0.26 -0.06 
15:OO 68 98 30 78.0 -1.0 123.1 0.26 -0.05 
- - 
10, Female Weightz2.58 kg Injection Time=6.0 secs 
Amount 1njected=2,6 ml 
OO:OO 50 89 39 63.0 0.0 165.5 0.85 0.36 
OO:O2 50 90 40 63.3 0.7 165.5 0.83 0.37- 
00:04 50 90 40 63.3 1.5 160.0 Om87 0.45 
00:06 50 90 40 63.3 1.5 160.0 0.90 0.51 
00:08 50 90 40 63.3 1.2 165.5 0.91 0.51 
00: 10 49 90 41 62.7 
1.1 165.5 0.87 0.51 
OO:12 49 89 40 62.3 
1.2 160.0 0.85 0.51 
OO: 14 49 88 39 62.0 
1.0 
- - 
- 
APPENDIX ( Continued) 
TIME DP SP PP MAP CVP HR R T 
11, 05:OO 72 99 27 81.0 0.7 126.3 0.32 0.00 
05:30 71 99 28 80.3 0.7 129.7 0.31 0.00 
06:OO 72 IOO 28 81.3 0.6 126.3 0.32 OeOO 
06:30 73 99 26 81.7 0.5 126.3 0.33 0.00 
O7:OO 73 98 25 81.3 0.2 126.3 0.32 0.00 
07:30 72 99 27 81.0 0.2 126.3 0.32 
0.00 
08:OO 71 99 28 80.3 0.1 126.3 0.33 0.00 
08:30 72 99 27 81.0 0.2 123.1 0.32 0.00 
O9:OO 71 98 27 80.0 0.1 126.3 0.32 0.00 
09:30 71 98 27 80.0 0.2 126.3 0.31 0.00 
IO.00 71 97 26 79.7 0.0 123.1 0.33 0.00 
10:30 71 97 26 79.7 0.2 - - - 
11:OO 70 96 26 78.7 -0.1 123.1 0.32 0.01 
11:30 71 96 25 79.3 -0.1 120.0 0.31 0.01 
12:OO 70 95 25 78.3 0.0 12000 0.32 0.01 
12:30 70 95 25 78+3 -0.2 120.0 0.32 0.01 
13:oo 70 95 25 78.3 -0.2 120.0 0.30 0.01 
13:30 70 95 25 78.3 -0.6 120.0 0.32 0.01 
14:OO 70 95 25 78.3 -0.7 120.0 0.31 O*Ol 
14:30 70 94 24 78.0 -0.5 120.0 0.32 0.01 
15:oo 70 94 24 78.0 -Oh5 117.1 0.31 oeol 
12. Male Weight=5,93 kg Injection Time= 16.0 secs - - 
Amount Injected=5.9 rnl 
72 
APPENDIX ( Continued) 
TIME 
12. 00:40 
00: 42 
00 : 44 
00: 46 
00 :.48 
00: 50 
00 : 52 
00: 54 
00:56 
OO1! 58 
01:oo 
01:lO 
01:20 
01 230 
01:40 
01:50 
02:oo 
02: 30 
CVP 
APPENDIX (Continued.) 
1 Male Weight=1.97 kg Injection Time=9.5 secs 
Amount Injecte&2.0 ml 
TIME 
00 : 00 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00:24 
MAP CW 
APPENDIX ( Continued) 
- - 
CVP 
TIME MAP 
APPENDIX (Continued.) 
15. Male (Neutered) Weight=4.50 kg 
Injection Time=7,0 secs Amount Injected=4.5 ml 
TIME DP 
00:OO 46 
00:02 46 
00:04 47 
00:06 49 
00:08 49 
0O:lO 46 
00:12 45 
00:14 46 
00:16 46 
00:18 46 
00:20 46 
00:22 48 
00:24 47 
00:26 48 
00: 28 49 
00:30 49 
00~32 48 
00:34 48 
00:36 49 
00:38 49 
00~40 49 
00:42 48 
00:44 48 
00:46 48 
MAP 
APPENDIX (Continued) 
TIME DP SP PP MAP CVP HR R T 
- - 
16. Male (~eutered.) Weight=4.39 kg 
Injection Tirne=22.5 secs Amount Injected=4.4 rnl 
APPENDIX ( Continued.) 
TIME MAP 
104.3 
104.3 
104.7 
104.3 
104.3 
104.3 
104.3 
104.3 
104.3 
104.3 
104.7 
104.3 
104.0 
104.3 
104.0 
104.3 
103.3 
104.3 
104.0 
105.3 
104.7 
105.0 
104.7 
104.7 
104.7 
106.3 
106.7 
107.7 
107.7 
109.3 
109.0 
108.7 
110.0 
109mO 
110.0 
109.0 
108.0 
108.7 
CVP 
APPENDIX ( Continued) 
DMSO Treatment Data 
17. Female Weight=4,24kg 
Injection Time= 14.0 secs Amount Injected.=4.2 ml 
TIME 
0o:oo 
00:02 
00:04 
' 00:06 
00 : 08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00: 24 
00: 26 
00: 28 
00:30 
00: 32 
00: 34 
00:36 
00: 38 
00: 40 
00 : 42 
00:44 
00: 46 
00: 48 
00: 50 
00: 52 
00: 54 
00: 56 
00: 58 
01 :oo 
01 : 10 
01:20 
01:30 
01:40 
01:50 
02:oo 
02: 30 
03:OO 
03: 30 
04:OO 
04: 30 
SP PP MAP 
122 57 84.0 
CVP 
1.5 
1.4 
1.5 
1.6 
2.7 
2.2 
3.0 
3.2 
4.0 
4.2 
4.7 
5.0 
5.4 
5.7 
5.9 
6.4 
7.0 
7.0 
7.0 
7.2 
6.7 
7.5 
7.2 
7.2 
7.1 
7.2 
7.1 
7.3 
7.2 
7.5 
7.2 
6.7 
6.2 
6.5 
6.4 
6.0 
5.7 
7.0 
7.0 
7.2 
7.5 
6.5 
APPENDIX ( Continued.) 
TIME DP SP PP MAP CVP HR R T 
17. 05~00 66 123 57 85.0 6.7 70.6 0.14 -0.09d 
05~30 67 125 58 86.3 6.2 70.6 0 -Om10d 
06:OO 69 
127 58 88.3 6.2 
68.6 0.16 -0,Ogd 
06:30 74 130 56 92.7 6.0 68.6 0.15 -0. IOd 
07:OO 71 130 
59 90.7 5.5 
68.6 0.16 0.09d 
07:30 77 135 58 96.3 5.7 70.6 0.18 0.09d 
08:OO 76 135 
59 95.7 5.2 70.6 0.17 0.09d 
08:30 79 137 58 98.3 5.2 70.6 0.18 0.09d 
09:OO 77 140 63 98.0 5.2 68.6 0.18 0.09d 
09:30 79 140 61 99.3 5.2 68.6 0.18 0.10d 
10:OO 82 145 
63 103.0 5.2 68.6 0.18 0.12d 
10:30 84 145 61 104.3 4.7 68.6 0.19 0.lOd 
11:OO 85 150 65 106.7 
4.7 - 
- - 
11:30 85 150 65 106.7 4.6 68.6 0.18 0.07d 
12:OO 86 154 68 108.7 4.7 68.6 0.18 0.09d 
1230 90 155 65 111.7 4.7 69.6 0.18 0.09d 
13:OO 90 157 67 112.3 4.6 69.6 0.18 0.10d 
13:30 95 163 68 117.7 4.5 67.6 
0.19 0.lOd 
14:OO 94 162 68 116.7 4.2 70.6 0.19 0.09. 
14:30 96 165 69 119.0 4.2 70.6 
0.18 0.10 
15:OO 99 166 67 121.3 4.0 69.6 0.18 0,iO 
- - 
18, Female Weight=3.78 kg Injection Time= 12.5 secs 
Amount Injected.=3.8 ml 
d.=d.iphasic T value 
APPENDIX ( Continued.) 
TIME 
MAP 
57.0 
60.7 
62.7 
65.0 
66.7 
66.7 
66.7 
66.0 
67.3 
66.7 
66.7 
67.0 
67.0 
65.3 
68.0 
69.7 
69.0 
67.0 
68.7 
71.3 
72.0 
74.3 
72.3 
70.7 
71aO 
73.7 
72.7 
73.3 
76.3 
76.7 
74.7 
76.3 
79.0 
78.0 
76.7 
75.3 
78.0 
78.3 
77.3 
76.0 
80.7 
80.0 
78.3 
CVP 
- 
2.0 
2.2 
2.0 
2.2 
2.5 
2.7 
2. 7 
3.0 
2.7 
3. 2 
3.0 
3. 5 
4.0 
4.5 
5.0 
6.0 
6.0 
6.0 
5.2 
5.0 
4.5 
4.5 
4.0 
3.7 
3.2 
3.7 
3.2 
3.0 
3.0 
3.2 
2.9 
2. 7 
2. 7 
2.7 
2.7 
2. 7 
2.7 
2.5 
2.6 
2.2 
2.5 
3.0 
2.7 
APPENDIX ( Continued.) 
19. Female WeighL3.52 kg 
Injection Time=5.5 secs Amount Injected=3.5 ml 
TIME DP SP PP MAP CVP HI3 R T 
APPENDIX (Continued.) 
TIME DP SP PP MAP CVP HR R T 
Female Weight=3,40 kg 
Injection Tirne=30.0 secs Amount Injected=3,4 ml 
84 
APPENDIX (Continued) 
TIME DP SP PP MAP CVP HR R T 
APPENDIX ( Continued.) 
21. Female Weighk3.25 kg 
Injection Time= 15.0 secs Amount Injected=3.2 ml 
TIME 
00 : 00 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00: 24 
00: 26 
00: 28 
MAP 
74.7 
75.3 
75,o 
77.3 
76.3 
74.0 
65.0 
58.3 
51.3 
47.3 
41 a7 
39.7 
33.7 
33.0 
36.0 
38.3 
40.0 
42.0 
43.3 
45.0 
47.3 
48.7 
50.7 
52.3 
54.0 
56.7 
58.0 
59.7 
60.3 
61.0 
62.0 
59.7 
56.7 
54.7 
52.3 
51.3 
51.7 
50.7 
51.7 
50.0 
52.7 
58.7 
CVP 
0.7 
1 a2 
1 .2 
1.7 
2. 5 
3.0 
3.2 
3.7 
4.2 
4.9 
6.0 
6.7 
7.5 
8.0 
8.5 
8.6 
8.5 
8.7 
8.7 
8.7 
8.2 
8.2 
8.0 
8.0 
7.8 
7.7 
7.7 
8.0 
7.6 
7.7 
7.7 
7.7 
8.0 
8.2 
8.2 
8.1 
7.5 
7.5 
7.0 
6.2 
5.5 
5.2 
APPENDIX ( Continued) 
TIME DP SP PP MAP CVP 
88 
APPENDIX (Continued.) 
23. Female Weighk3.15 kg 
Injection Time=6.5 secs Amount Injected=3.1 ml 
TIME 
0o:oo 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00: 24 
00: 26 
00: 28 
00: 30 
00: 32 
MAP 
53.0 
53.0 
54.0 
54.0 
53.0 
50.3 
48.3 
47.0 
47.0 
42.7 
39.0 
CVP 
02:30 41 71 30 51.0 
03~00 40 74 34 51.3 
03:30 43 75 32 53.7 
04~00 43 75 32 53.7 
04:30 45 79 34 56.3 
**Elevated S-T segment 
APPENDIX ( Continued.) 
TIME DP SP PP MAP CW HR R T 
23. 05~00 45 76 31 55.3 4.2 123.1 0.61 -0.03** 
05~30 45 82 37 57.3 4.0 123.1 0.62 -0.04"" 
06:OO 46 82 36 58.0 4.0 126.3 0.61 -0.03** 
06:30 49 85 36 61.0 3.7 123.1 0.61 -0a02** 
07:OO 49 85 36 61.0 3.7 126.3 
6 -OaO3** 
07:30 50 86 36 62.0 
3.5 120.0 0.64 -0.02** 
08:OO 50 89 39 63.0 3.0 123.1 
0.63 -0.03** 
08:30 50 89 39 63.0 3.0 123.1 
0.63 -0.04** 
09:OO 50 90 40 63.3 2.9 123.1 0.63 -0.04** 
09:30 50 90 40 63.3 2.7 
123.1 0.62 -0.04** 
1O:OO 50 90 40 63.3 2.7 126.3 
0.61 -0,04** 
10:30 50 91 41 63.7 2.5 123.1 
0.61 -0.04** 
11:OO 50 91 41 63.7 2.5 126.3 
0.65 -0.03** 
11:30 50 93 43 64.3 2.5 126.3 
0.65 -0.04** 
12:OO 50 94 44 64.7 2.5 126.3 
0.66 -0.04** 
12:30 52 95 45 67.0 2.5 123.1 
0.65 -0.03** 
13:OO 50 94 44 64.7 2.5 123.1 
0.65 -0.04** 
13~30 51 95 44 65.7 2.5 
123.1 0.65 -0.03** 
14:OO 51 94 43 65.3 
2.0 
- - - 
14~30 50 94 44 64.7 1.9 - - 
- 
15:OO 50 90 40 63.3 2.1 126.3 0.56 -0.03** 
- - 
24. Female Weighk2.85 kg 
Injection Time=14.5 secs Amount Injected=2.8 ml 
00:/8 17 26 9 20.0 
**E evated. S-T segment 
APPENDIX (Continued) 
TIME 
MAP CVP 
9 1 
APPENDIX ( Continued.) 
25. Female Weighk2.78 kg 
Injection Time= 12.0 sees Amount Injectedz2.8 ml 
TIME DP SP 
92 
APPENDIX ( Continued.) 
TIME DP SP PP MAP CVP I-IR R T 
25. 05:OO 88 137 49 104.3 1 184.6 0.33 0.22 
05:30 88 135 47 103.7 3.5 177.8 0.36 0.21 
06:OO 86 13.5 49 102.3 3.1 184.6 0.36 0.22 
06:30 85 137 52 102.3 3.1 184.6 0.36 0.21 
07-:00 87 143 56 105.7 4.2 - - - - 
07:30 85 147 62 105.7 4.7 - - 
08:OO 83 145 62 103.7 4.6 181.6 0.33 0.19 
0830 82 146 64 103.3 4.6 184.6 0.33 0.18 
09:OO 79 150 71 102.7 4.5 184.6 0.34 0.16 
09:30 78 149 71 101.7 4.0 184.6 0.28 0.15 
1O:OO 75 145 70 98.3 4.4 184.6 0.33 0.16 
10:30 77 150 73 101.3 3.8 184.6 0.28 0.15 
11:OO 76 149 73 100.3 3.2 184.6 0.27 0.15 
11:30 77 149 72 101.0 3.1 192.0 0.28 0.15 
12:OO 77 146 69 100.0 3.4 184.6 0.30 0.15 
12:30 77 143 66 99.0 2.7 184.6 0.31 0.16 
13:OO 78 144 66 100.0 3.0 192.0 0.25 0.15 
13:30 81 147 66 103.0 2.9 192.0 0.28 0.15 
14:OO 83 145 62 103.7 2.4 184.6 0.28 0.16 
14:30 79 140 61 99.3 2.6 184.6 0.28 0.16 
15:OO 83 144 61 103.3 3.7 184.6 0.33 0.18 
26. Female Yieight=2.70 kg 
- - 
Injection Tirne=8.0 secs Amount InjecterL2.7 ml 
0O:OO 74 100 26 82.7 1.7 133.3 0.37 0.02 
00:02 75 100 25 83.3 2.7 133.3 0.42 0.02 
00~04 75 100 25 83.3 3.2 133.3 0.39 0.01 
00:06 76 101 25 84.3 3.5 133.3 0.42 0.00 
00:08 71 99 28 80.3 3.6 133.3 0.45 0.02 
0O:lO 65 92 27 74.0 3.7 133.3 0.50 0.01** 
** 
00:12 61 87 26 69.7 
3.7 133.3 0.55 0.03** 
00:14 55 82 27 64.0 4.2 133.3 0.60 0.02 
** 
00:16 - 49 75 26 57.7 4.4 133.3 0.60-- 0.03** 
00:18 43 70 27 52.0 4.5 133.3 0.56 0.02 
00:20 41 66 25 49.3 4.5 133.3 0.60 0.01** 
00:22 40 65 25 48.3 4.5 133.3 0.57 0.02,** 
00~24 39 64 25 47.3 
4.1 
- - - 
** 
00:26 40 64 24 48.0 4.0 126.3 0.55 O.Ol** 
00:28 40 65 25 48.3 3.7 129.7 0.52 0.01 
00:30 41 66 25 49.3 3.6 129.7 0.55 O.Ol** 
00:32 42 69 27 51.0 3.7 129.7 0.60 0.01** 
00:34 44 68 24 52.0 3.2 129.7 
0.55 0.01** 
00:36 45 73 28 54.3 3.5 129.7 0.65 0.00~-- 
00:38 47 74 27 56.0 3.0 126.3 0.55 0.01** 
**Elevated S-T segment 
93 
APPENDIX ( Continued) 
TIME DP SP PP MAP 
08:30 83 111 28 92.3 
09:OO 85 115 30 95.0 
09~30 85 115 30 95.0 
1O:OO 87 116 29 96.7 
10:30 89 118 29 98.7 
11:OO 86 116 30 96.0 
11:30 88 118 30 98.0 
12:OO 85 115 30 95.0 
12:30 90 118 28 99.3 
13:OO 87 117 30 97.0 
13:30 89 118 29 98.7 
14:OO 87 117 30 97.0 
14~30 90 119 29 99.7 
15:OO 89 119 30 99.0 
**Elevated S-T segment 
APPENDIX (Continued.) 
27. Female Weightz2.60 kg 
Injection Tirne=8.5 secs Amount Injectedz2.6 ml 
TIME 
0o:oo 
00:02 
00:04 
00:06 
00:08 
00: 10 
00: 12 
00: 14 
00: 16 
00: 18 
00: 20 
00: 22 
00:24 
00: 26 
00: 28 
00 : 30 
00:32 
00 : 34 
00: 36 
00:38 
00:40 
00: 42 
00:44 
00:46 
00:48 
00: 50 
00: 52 
00:54 
00:56 
00:58 
01:oo 
01: 10 
01:20 
01:30 
01:40 
01:50 
02:oo 
02: 30 
03:OO 
03: 30 
04:OO 
04: 30 
SP PP MAP 
95 
APPENDIX (Continued) 
TIME DP SP PP MAP CVP HR R T 
27. 05:OO 55 100 45 70.0 4.0 150.0 0.60 -0.24 
05:30 55 100 45 70.0 4.5 150.0 0.60 -0.18 
06:OO 53 96 43 67.3 4.2 150.0 0.75 -0.27 
O6:30 52 95 43 66.3 4.2 150.0 0.57 -0.24 
07:OO 52 95 43 66.3 4.2 150.0 0.58 -0.27 
07:30 51 93 42 65.0 4.2 150.0 0.56 -0.24 
08:OO 50 92 42 64.0 4.0 150.0 0.54 -0.27 
O8:3O 50 91 41 63.7 4.2 150.0 0.57 -0.30 
09:oo 50 91 41 63.7 4.0 150.0 0.61 -0.18 
09:30 50 89 39 63.0 4.0 150.0 0.54 -0.27 
10:OO 50 90 .40 63.3 4.2 150.0 0.51 -0.24 
10:30 50 90 40 63.3 4.2 150.0 0.57 -0.30 
11:OO 50 90 40 63.3 4.0 150.0 0.54 -0.24 
11:gO 50 90 40 63.3 4.2 150.0 0.51 -0.33 
12:OO 50 90 40 33 4.0 - 0.51 -0.30 
12:30 49 88 39 62.0 4.2 150.0 0.51 -0.28 
13:oo 48 89 41 61.7 4.0 150.0 0.46 -0.36 
13:30 49 89 40 62.3 4.0 150.0 0.52 -0.36 
14:oo 46 87 41 59.7 4.5 150.0 0.48 -0.31 
14:30 45 87 42 59.0 
4.4 150.0 0.48 -0.33 
15:OO 45 87 42 59.0 
4.2 150.0 0.42 -0.39 
28. Male lX/eight=2.58 kg 
Injection Tirne~5.5 secs Amount ~njected-2.6 ml - - 
OO:OO 50 90 40 63.3 1.5 133.3 0.41 O*O4d 
OO:O2 50 90 40 6 2.5 133.3 0.37 0.04d 
00:04 53 88 35 64.7 3.0 133.3 0.48 0.04d- 
OO:O6 54 92 38 66.7 2.5 133.3 0.40 O*O3d 
00:08 53 90 37 65.3 2.5 137.1 0.46 -0.05d" 
00: 10 54 90 36 66.0 2.2 137.1 0.49 -0.11d" 
00: 12 50 82 32 60.7 2.2 137.1 0.54 -0.07d" 
00:14 44 77 33 55.0 2.5 133.3 0.49 -0.05d" 
00:16 40 74 34 51.3 3.0 137.1 0.46 T0.04d* 
00:18 8 70 32 48.7 3.0 133.3 0.48 -$)*03&* 
00:20 37 70 33 48.0 3.0 133.3 0.48 -O*O3d* 
OO:22 37 69 32 47.7 3.0 133.3 0.46 0.03" 
00~24 38 71 33 49.0 2.7 133.3 0.44 O.O2* 
00~26 39 72 33 50.0 2.5 129.7 0.42 0.04" 
00:28 40 75 35 51.7 2.5 133.3 0.56 -0.05d" 
00~30 41 75 34 52.3 2.0 133.3 0.44 0.04" 
00~32 43 80 37 55.3 1.8 133.3 0.53 O*O4* 
00:34 45 80 35 56.7 1.7 133.3 0.44 0.03" - 
OO:36 45 84 39 58.0 1.7 133.3 0.48 +O.O2* -- 
00:38 46 85 39 59.0 1.7 133.3 0.43 -o.old*-- 
d=diphasic T value 
"Depressed S-T segment 
APPENDIX (Continued.) 
TIME DP SP PP MU CVP m 
-0.03d." 
-0.04d." 
-0 04d." 
-0.04" 
-0.02d."-- 
-0.04d." 
+ 
-0.02d" 
+ 
-0.0 1 d." 
-I- -0.01d* 
+ 
-0.0 1 d." 
0.026" 
0.02d.** 
-0.02d"" 
-I- 
-0.01 d." 
-0.02d.*je 
+ 
-0.0 1 d."" 
+ 
-0.0 1 d."" 
O.O2d.** 
-0*02d** 
+ 
-O.Old.** 
-0.02d."" 
+ 
-O.Old.*" 
d=Diphasic T value 
"Depressed. S-T segment 
""Elevated. S-T segment 
APPENDIX ( Continued.) 
29. Male Weight=2.37 kg 
Injection Time=5.5 secs Amount Injected= 
TIME DP SP PP MAP 
00:32 50 80 30 60.0 
00:34 54 84 30 64.0 
00:36 56 87 31 66.3 
00:38 58 90 32 68.7 
00:40 60 91 31 
70.3 
00:42 61 94 33 72.0 
00:44 61 9433 72.0 
00:46 61 94 33 72.0 
00:48 61 95 34 
72.3 
00:50 62 
95 33 73.0 
00:52 62 95 33 73.0 
00:54 61 94 33 72.0 
00:56 60 94 34 
71.3 
00:58 60 93 33 71.0 
0l:OO 60 92 32 
70.7 
0l:lO 59 91 32 69.7 
01:20 60 94 34 
71.3 
01:30 60 93 33 71.0 
01:40 60 91 31 
70.3 
01:50 59 90 31 69.3 
02:OO 60 90 30 70.0 
02:30 61 91 30 71.0 
03:OO 69 97 28 78.3 
03:30 74 100 26 82.7 
04:OO 74 101 27 83.0 
04:30 75 102 27 84.0 
"Depressed S-T segment 
CVP 
98 
APPENDIX (Continued.) 
TIME DP SP PP MAP CVP HR R T 
30. Male (~eutered.) lkVeight=5. 2 kg 
Injection Time=21.0 secs Amount Injected.=5.3 ml - - 
"Depressed. S-T segment 
d.=Diphasic T value 
APPENDIX ( Continued.) 
TIME DP SP PP MAP 
CVP 
13:30 80 113 33 
14:OO 78 110 32 
14:30 74 113 39 
15:OO - - - 
d.=Diphasic T value 
APPENDIX ( Continued.) 
31 . Male (Neutered.) Weight=5.17 kg 
Injection Time= 15.0 secs Amount Injected=5.2 ml 
TIME DP SP PP 
02:30 47 75 28 
03:OO 50 76 26 
03:30 50 81 31 
O4:OO 52 84 32 
04:30 55 87 32 
d=Diphasic T value 
MAP CVP HR 
APPENDIX Continued.) 
TIME DP SP PP MAP CVP HR R T 
31. 05:OO 59 92 33 70.0 6.0 109.1 0.84 -0.06 
05:30 59 93 34 70.3 5.2 109.1 0.83 -0.06 
06:OO 60 94 34 71.3 5.2 109.1 0.83 -0.04 
06:30 64 97 33 75.0 5.5 109.1 0.84 -0.06 - 
07:OO 64 97 33 75.0 5.0 106.7 0.91 -0.07 
07:30 64 98 34 75.3 5.0 109.1 0.90 -0.07 
08:OO 65 101 36 77.0 5.0 106.7 0.87 -0.06 
08:30 65 101 36 77.0 5.0 106.7 0.90 -OaO5 
09:OO 66 102 36 78.0 5.0 109.1 0.90 -0.05 
09:30 66 102 36 78.0 4.7 109.1 0.91 -0.06 
1O:OO 68 103 35 79.7 4.7 109.1 0.90 -OaO5 
10:30 69 105 36 81.0 4.5 106.7 0.93 -0.05 
1I:OO - - - - 4.5 106.7 0.93 -0.05 
11:30 69 105 36 81.0 4.5 106.7 0.91 -0.04 
12:OO 70 106 36 82.0 4.7 109.1 0.96 -0.06 
12:30 70 107 37 82.3 4.5 106.7 0.97 -0.03 
13:OO 70 108 38 82.7 4.2 109.1 0.96 -0.05 
13~30 70 107 37 82.3 4.0 109.1 0.99 -0.04 
14:OO 70 106 36 82.0 4.0 109.1 1.06 -0.03 
14:30 70 107 37 82.3 4.2 109.1 
0.99 -0.06 
15:OO 69 105 36 81.0 4.2 109.1 0.98 -0.07 
- - 
32. Male (Neutered) Weight=4.38 kg 
Injection Tirne=7 secs Amount Injected=4.4 ml 
00: 18 24 35 11 
00:20 24 35 11 
00:22 24 34 10 
00:24 22 32 10 
00:26 23 33 10 
00:28 22 32 10 
00:30 21 31 10 
00:32 20 30 10 
00:34 20 28 8 
00:36 19 26 7 
00:38 17 24 7 
d.=Diphasic T value 
APPENDIX ( Continued.) 
TIME DP SP PP MA9 
14:30 94 113 19 100.3 
15:oo 92 111 19 98.3 
d=Diphasic T value 
*Depressed S-T segment 
CVP 
5.0 
5.0 
5.0 
40 8 
4.7 
5.0 
5.0 
5.0 
5.0 
5.0 
5.0 
5.1 
5.4 
5.5 
6.0 
6.2 
5.7 
6.5 
6.7 
4.2 
3.7 
3.7 
3.2 
3.0 
2.8 
2.5 
2.5 
2.7 
1.2 
1.7 
1.7 
1.5 
1.7 
2.0 
1.7 
1.7 
1.7 
1.1 
1.0 
1.1 
1.1 
1.1 
1.0 
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