A programmable physiological infusion device and method are provided wherein a program source, such as a paper tape, is used to actuate an infusion pump in accordance with a desired program. The system is particularly applicable for dispensing calcium in a variety of waveforms

Adachi, R. R.

Howard, W. H.

Young, D. R.

English

NASA Technical Reports Server

REPLY TO
ATTN OF: GP
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
WASHINGTON, D.C. 20546
MAY 2 2 1974
TO: KSI/Scientific & Technical Information Division
Attn: Miss Winnie M. Morgan ~~
FROM: GP/Office of Assistant General
Counsel for Patent Matters
SUBJECT: Announcement of NASA-Owned U.S. patents in STAR
In accordance with the procedures agreed upon by Code GP
and Code KSI, the attached NASA-owned U.S. Patent is being
forwarded for abstracting and announcement in NASA STAR.
The following information is provided:
U.S. Patent No. :
Government or
Corporate Employee
Supplementary Corporate
Source (if applicable)
NASA Patent Case No.
G? tsy\ <?v\T
- I °i <(•<( 7 -
NOTE - If this patent covers an invention made by a corporate
employee of a NASA Contractor, the following is applicable:
YES NO /y?
Pursuant to Section 305(a) of the National Aeronautics and
Space Act, the name of the Administrator of NASA appears on
the first page of the patent; however, the name of the' actual
-inventor -(author) -appears -at -the~headinq of column Nbv.: 1 of
the Specification, following the words " . r S t o a e c t to
an invention of ..."
Bonnie L. Woerner
Enclosure
https://ntrs.nasa.gov/search.jsp?R=19740014658 2020-03-17T14:41:13+00:00Z
United States Patent
Howard et al.
[19] [in 3,809,871
[45] May 7, 1974
[54] PROGRAMMABLE PHYSIOLOGICAL
INFUSION
[75] Inventors: Wayne H. Howard, Mountain View;
Donald R. Young, Los Altos Hills;
Richard R. Adachi, Menlo Park, all
of Calif.
[73] Assignee: The United States of America as
represented by the Administrator of
the National Aeronautics and Space
Administration, Washington, D.C.
[22] Filed: Dec. 1,1972
[21] Appl. No.: 311,175
[52] U.S. Cl 235/151.3, 128/214 E
[51 ] Int. Cl G06f 15/42, A61m 5/14
[58] Field of Search 235/151.3, 151.34;
128/213, 214 E . 2 1 4 F
[56] References Cited
UNITED STATES PATENTS
3,043,303 7/1962 Still 128/214 E
2,690,178 9/1954
3,655,095 4/1972
3,700,904 10/1972
Bickford ............................. 128/213
Kienitz ........................ 128/214 E X
Stobble et al ............... 128/214 E X
Primary Examiner — Malcolm A. Morrison
Assistant Examiner — Jerry Smith
Attorney, Agent, or Firm— Armand G. Morin, Sr.; Dar-
rell G. Brekke; John R. Manning
[57] ABSTRACT
A programmable physiological infusion device and
method are provided wherein a program source, such
as a paper tape, is used to actuate an infusion pump in
accordance with a desired program. The system is par-
ticularly applicable for dispensing calcium in a variety
of waveforms.
The invention described herein was made by
employees of the United States Government and may
be manufactured and used by or for the Government
for Governmental purposes without the payment of
any royalties thereon or therefor. *
5 Claims, 4 Drawing Figures
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SHEET 1 OF 4
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COMPUTER
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SHEET 2 OF 4
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PROCESSING
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^ATENTEO NAY 3.809.871
SHEET 3 OF 4
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3,809,871
1
PROGRAMMABLE: PHYSIOLOGICAL INFUSION
BACKGROUND OF THE INVENTION
1.. Fieldiof the invention-
, Programmable infusion system for animal experi- 5
ments.
2. Description of the prior art
Previous methods of infusion involved a rapid injec-
tion.in a single dose with a hypodermic syringe or a pro-
tracted injection at a constant rate with a pumping de- 10
vice: Neither system provides for the elucidation of the
control mechanism: in body chemistry, particularly in
calcium regulation. Suchrsystems as have been usedJn.
the; past emphasize only the steady state relationships
between the variables of interest while the present'in- 15
vention provides for testing physiologic systems to de-
velop functional relationships from the. data obtained.
This is particularly important when studying, the uri-
nary disposal and tissue distribution of calcium.
SUMMARY OF THE INVENTION
The purpose of this invention is to provide a device
which will infuse a substance at a rate which varies in
time and following a preprogrammed curve. This in-
vention is a rate programmable: pump system and in-
volves the concept of rate programmed infusion.
In the basic bioscience area, such a device is needed
to determine the ways in which the body systems are
capable of responding to dynamic chemical inputs. It is
illuminating.to apply a step function waveform infusion
to be: able to examine, in an animal, the. nature of the
physiological response: and its frequency content. Peri-
odic.inputs are:necessary for reproducing.or simulating
natural time-varying inputs and the pulsatile: nature of
many processes, and. to examine the. frequency, phase
and amplitude characteristics of the responding system.
For some biological investigations, less severe inputs
which are more consistent with physiological perform-
ance.may be obtained by ramp inputs. The programma-
ble^feature of the. device.makes it useful for controlling,
the: dispensing of fluid as a function of time.
The present invention is particularly applicable to a
system capable of dispensing, calcium, in a variety of
waveforms or forcing conditions. The purpose of this
invention is to evaluate the properties of the blood cal-
cium regulatory system in animals. The sinusoidal time-
varying input of calcium is one.of the functions selected
for testing. Historically, the sinusoidal time-varying
input has been used for evaluation of the properties of
mechanical systems. It is useful in testing for linear
characteristics of systems; the magnitude and phase of
the: response: provides numerical values for the damp-
ing-ratios. And, for the present applications, a compari-
son of amplitudes and angular frequencies of the blood
calcium response with the. sinusoidal calcium input pro-
vides critical data relevant to the. performance and con-
trol features of the blood calcium regulatory system.
The. component parts of the preferred programmed
pumping system consist of the following:
1. computer program and resulting, printed, paper
tape.
2. photoelectric, tape, reader
3. signal conditioner
4-. solenoid, operated piston pump such as a Harvard
lambda pump.
When the system is in operation, the curve represent-
ing, the desired waveform for infused calcium is read.as
20
25
35
40
45
50
marks on a continuous loop of paper tape. The marks
are printed by a computer on the .paper tape in such a
way that a pulse modulated curve results at the output
when the: tape, is run through a photoelectric reader at
a constant speed. After a mark on the paper tape is
sensed, the signal is conditioned to operate the solenoid
equipped piston pump that pumps a desired infusion
substance into a vein of an animal.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. I is a flow diagram showing the steps performed
in a preferred embodiment of the invention.
FIG. 2 is a similar flow diagram showing a simulator
for testing the accuracy of the present invention.
FIG. 3 is a graph illustrating the effect of sinusoidal
injection of calcium on blood calcium and urine cal-
cium.
FIG. 4 is a similar diagram showing the results ob-
tained by the prior art wherein calcium is infused at a
steady rate.
DESCRIPTION OF THE PREFERRED
EMBODIMENTS
Referring now to FIG. 1 of the drawing, a flow dia-
gram is shown of a preferred method of practicing the
present invention. In accordance with this embodi-
ment, a computer program.at 1 is developed to an out-
put desired waveform such as a sinusoidal wave. The
method of doing this is set forth in detail later. The out-
put of the. program is fed into a teletype terminal 3
which provides a printed tape 5 having thereon a series
of pulses or lines wherein the distance between the
pulses represent the number of pump strokes necessary
to provide the desired area under the curve. A photoe-
lectric reader 7 is employed to read the pulses and the
pulses are amplified to a suitable level in a signal condi-
tioner 9 and the pulses fed to an infusion pump 11. The
preferred photoelectric tape reader is photoswitch type
22DJ4 made by Electronics Corporation' of America,
Cambridge, Massachusetts; the preferred signal condi-
tioner is a conventional pulse multiplier designed to
give 1-10 output pulses for each input pulse; and the
preferred. infusion pump is a Harvard lambda pump
made by the Harvard Apparatus Company of Dover,
Massachusetts. The infusion pump is connected to an
experimental animal 13 and blood samples are periodi-
cally taken and analyzed at 15. Normally urine samples
would also be taken and analyzed but this is not illus-
trated.
In FIG. 2 a simulator is shown for testing the system
of the present invention. Here the phototape reader 7
feeds pulses to the piston actuated infusion pump 11.
The infusion pump is connected to a source of a solu-
tion of calcium chloride 17 and the effluent from the
pump is taken through line 19 and mixed with a con-
stant flow of saline solution from a source 21 and
passed to an automatic fraction collector 23 where the
solution is divided into samples and passed to an atomic
absorption spectrophotometer 25 for the analysis of
calcium. The data from the spectrophotometer is pro-
cessed at 27 and plotted as a curve 29. On the graph,
the values of calcium in each of the samples have been
plotted. In one practical test of the equipment, wherein
5 miJHter samples were collected from the automatic
fraction collector, the variation between the observed
and expected calcium content of each fraction was only
± 0.0005 mg.
3,809,871
3 4 ^
FIGS. 3 and 4 illustrate the results obtained with the a space on the tape and suitable ascil characters to
present invention. punch in the eight channels. This would provide for up
For the tests on anesthetized Rhesus monkeys, cal- to eight channels to carry waveforms, providing multi-
cium gl'ucoheptonate was infused into a saphenous vein P'e channel operation and simultaneous infusion of sev-
through a polyethylene Intracath. Blood and urine sam- 5 eral substances or for just the convenience of being
pies were taken at regular timed intervals and analyzed able to switch easily from one waveform to another
for calcium with an atomic absorption spectrophotom- witn sin8!e channel operation.
eter. Blood was withdrawn from the leg opposite to the The punched tape is read on a reader, such as the
infusion; urine was collected through a no. 6 French Friden Pulse driven ^P6 reader' *hich has the feature
ureteral catheter. FIG. 3 shows the total blood serum 10 °,f advan™>e °" th« command of a pulse or a switch
and urine calcium response to a sinusoidal infusion of c'osure: ™ls prO^te.S f°r C°nt™' ° -the %e'd °{^
,, ,_ r i • v. f i f n e u advancing tape and thus control the time of the run. A215 mg of calcium per hour for a total of 2.5 hr
 ica, ta
e
 advancement speed is about i character
To .ndicate damping and phase shiftmg in the blood ^
 second Anothef unh Js needed to be provided to
response, the sinusoid line, representing the calcium
 generate appropriate pulses or switch closures to the
infused in mg for each blood and urine sampling pe- 15 °eader
riod, has been included. For each sampling period, the
 Paper punched tape does not provide for ease of cor-
total mg of calcium in the urine is shown on top of the rection as does the photoelectric tape which needs only
serium calcium level. This displays the total appear-
 a pen or white paint. It is more difficult to make tapes
ance of calcium in the blood and urine in relationship
 wjtn a free form wave with punched tape. With the
to the infused calcium. 20
 pnoto tape free form waves can be scribed by hand with
FIG. 4 shows the result of a steady-rate infusion a pen.
(square wave) of 135 mg of calcium over 2 hr. with the Magnetic tape may also be used to substitute for the
subsequent fall of serum calcium after termination of photoelectric tape and drive with suitable electronic
the infusion, and again the urine calcium is shown on interfacing. As in the case of the paper punched tape,
top of the serum calcium level; the solid line indicates 25 this is more difficult to make corrections or free form
the infusion duration. waves.
The mode of operation has been described in detail We claim:
in regard to the specific problem of calcium homeosta- l- A method for studying body response to dynamic
sis although other applications are evident. Fre- pulsatile chemical inputs which includes infusing a sub-
quently, under both normal and disordered metabolic 30 stance into a test animal over a Period of time for rais'
conditions, blood calcium level is relatively constant. In in8 and lowering the concentration of said substance
humans, increased dietary calcium, intravenous admin- according to a sustained and predetermined wave form,
istration of nominal levels of calcium, or increased 'omprismg the steps of recording a desired program on
, , . . , .. an information carrying medium, wherein said programbone reircrpuon and osteopenia do no necessarily
 indudeg a ,se.modjjated wav'e form coded on said
modify blood calcium level. Therefore calcium is con-
 medium> sensing the pulses on said medium, feeding
trolled within a small range. A method is required to
 sajd sensed pu,ses to a solenoid piston infusion pump
provide a means to better evaluate calcium regulation.
 whereby said solenoid activated pump infuses predeter-
The method required would need to describe the dy-
 mjned arnounts of said substance into said animal, said
namics of the regulatory system, and to define the ef-
 amounts corresponding to and being dependent upon
feet of calcium level on the secretory function of glands 4O
 the iengtn and shape of said coded pulse-modulated
associated with calcium regulation. This would provide wave form.
information of value for diagnosis, prevention, or ther- 2. The method of claim 1 wherein said wave form is
apy. . • . a sinusoidal wave and said test substance is calcium.
In carrying out a preferred method of practicing the 3. An apparatus for infusing a substance into an ani-
present invention, a paper tape in a continuous loop 45 mal for raising and lowering the concentration of said
must first be made. This tape has marks scribed on it substance at a predetermined rate and in a sustained
at varying intervals depending on the desired waveform and predetermined wave form comprising in combina-
needed for infusion. The paper tape may be made by tion:
hand using a pen and ruler to scribe the marks. The in- a- a record of a desired infusion program, said pro-
tervals on the tape between the marks are computed. 50 8ram including a pulse-modulated wave form
coded on an information carrying medium,
A faster method to make the tape is to use a com- b- means for readin8 said pulse-modulated wave form
puter and a teletype terminal as is shown in FIG. 1. The record and for converting said record into a series
line feed on the terminal is used to space along the tape ,, ot pu ses, . . . . .
 e
and a dash to print the marks. The computer is faster » ^m^rTS XttS^JT "
and permits a number of tapes to be made ,n a short
 rf means for jnjecti ^ incremems of a test sub.
time. It is necessary also to be able to make tapes of dif-
 stance into an experimental animal,
ferent length and different numbers of marks to adjust
 4 Jhe apparatus of claim 3 wherein said program is
the time of the run and the total volume of fluid in-
 6Q in the form of a paper tape havjng a series of dashes
fused. These require that new tapes be contmuallly pro- thereon wherein the distance between said dashes rep-
duced. resents the time between desired infusion increments.
A paper punched tape, such as is used with teletypes
and computers along with suitable tape handling equip- 5. The apparatus of claim 4 wherein a photoelectric
ment, may be substituted for the photoelectric tape and
 65 reader is employed to read said tape and a solenoid-
drive. The paper punched tape may be made on a com- type piston pump is employed to translate said dashes
puter and teletype terminal in a similar manner as the into increments of test substance,
photoelectric tape, using the nul character to advance * * * * *


Programmable physiological infusion

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