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Description  |
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a means of measuring physiological
pressures, including blood pressure, intracranial pressure, intrapleural
(for evaluation of respiratory function and respiration rate) pressure,
pressure within the gastrointestinal system.
2. Description of the Prior Art
Laboratory animals are often used as models of human response to various
stimuli and pharmacological agents. Such models are used to project the
effect of pharmaceutical compounds, determine the toxicity of chemicals,
and to better understand human physiology.
Ony physiological parameter of interest in such evaluations is blood
pressure. In many cases, because blood pressure fluctuates with the time
of day and is episodic, it is necessary to obtain chronic and frequently
sampled measurement of blood pressure within a given animal in order to
assess the effects of an agent over a time course. There are several
methods which are currently used for chronic measurement of blood
pressure. These include the tail cuf method, chronic cannulation, the use
of implantable pressure sensors in combination with telemetry, and the use
of a vascular access port.
The tail cuff method is well developed with several manufacturers producing
such a device. In this case, the animal (usually a rat) is placed in a
restraining device. An inflatable cuff is placed on the tail. A blood flow
sensor (either plethysmographic or Doppler utrasound) is usually integral
to the cuff. The cuff is inflated until blood flow has ceased and is then
deflated. The first indication of pulsatile flow and the first indication
of continuous flow are noted as the systolic and diastolic pressures,
respectively. Some of these devices require that the arteries of the
animal be dilated by heating the entire body of the animal to 40.degree.
C. or more, causing significant stress on the animal and subsequent
artifact. Since these devices require that the animal be restrained,
artifact is introduced due to the stress of handling and restraint. In
addition, it is not possible to humanely obtain measurements from an
animal at frequent intervals with this method, and it is very labor
intensive.
Chronic cannulation is the most frequently used method for measurement of
blood pressure. With this method, a small catheter is inserted into an
artery, typically and carotid, descending abdominal aorta, or femoral
artery. The catheter is exteriorized at a point, typically on the back,
which generally prevents it from being destroyed by the animal. The
catheters from a number of animals may be connected to a single pressure
transducer through solenoid valves. A pump is typically used with each
animal to continuously backflush the catheter with a heparinized saline or
other anticoagulant solution. In addition, a swivel must be used on each
catheter to prevent it from becoming tangled as the animal moves about the
cage. The solenoid valves and pressure transducers are often connected to
a computer to allow frequent sampling of pressure from each animal. This
method has several disadvantages: First, since the catheter is long and
relatively small in diameter, the higher frequency components of the
pressure waveform are lost. Second, even though precautions are taken, the
animals often become tangled in the catheter or learn to grab the catheter
with their teeth or paws, and subsequently bleed to death. Third, keeping
the catheters patent requires considerable maintainance and is thus labor
intensive.
Implantable pressure sensors are sometimes used in combination with
telemetry. This eliminates some of the disadvantages pointed about above.
Konigsburg Instruments manufactures a sensor which is 3.5 mm in diameter.
However, this sensor is too large for many applications, and since it is
most frequently necessary to mount it in the wall of a vessel, it is
subject to fibrous tissue growth over the sensing diaphragm which results
in drift of the measured signal. In addition, the nature of the transducer
is such that drift is inherent and requires frequent in-vivo calibration.
Miniature solid state sensors mounted on the tip of a catheter have also
been used to measure internal body pressures. Some commercially available
devices are as small as 1 mm diameter. Because of the inherent instability
of these devices they require calibration within a short time prior to use
and are suitable only for acute measurements.
In larger animals (dogs, etc.), it is possible to implant a vascular access
port in the femoral artery. In this approach, a catheter is attached to a
reservoir opposite a diaphragm. The diaphragm can be pierced with a needle
connected to a pressure transducer when acquiring pressure measurements
and flushing the catheter. The disadvantage of this approach is that it is
labor intensive. A sterile protocol is required each time the diaphragm is
pierced. In addition, the catheter requires bi-weekly flushing in order to
maintain patentcy. If sterile protocol is broken, the animal may develop
infection, requiring expensive antibiotics and removal from the study
until the infection clears.
SUMMARY OF THE INVENTION
The present invention is an implantable pressure sensing device which
includes an implantable catheter means, implantable pressure sensing
means, and implantable osmotic infusion pump means. The catheter means has
its distal end placed at a position within the animal at which an internal
body pressure (such a blood pressure) is to be sensed. The pressure
sensing means is connected to the proximal end of the catheter, and
provides a signal which is a function of the internal body pressure. In
preferred embodiments, the pressure sensing means includes a pressure
transducer and a transmitter for transmitting a signal out of the animal
as a function of the sensed pressure. The osmotic infusion pump means is
connected to the proximal end of the catheter means and supplies doses of
an antithrombogenic solution through the catheter means to the distal end
to prevent or reduce clotting which would prevent pressure from being
sensed.
BRIEF DESCRIPTION OF THE DRAWINGS
The FIGURE shows a preferred embodiment of the implantable pressure sensing
device of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Pressure measurement device 10 shown in the FIGURE is a very small,
lightweight device which can be implanted into small animals, such as
rats, to provide chronic measurement of internal body pressures such as
blood pressure. Device 10 includes pressure sensing catheter 12, pressure
transducer 14, transmitter 16, osmotic infusion pump 18, catheters 20 and
22, check valve 24, access catheter 26, and flow restrictor 28.
As shown in the FIGURE, transducer 14 and transmitter 16 are contained
within housing 30. Nipple 32 at one end of housing 30 communicates with
pressure transducer 14 and is inserted into proximal end 34 of catheter
12. Distal end 36 of catheter 12 is inserted, for example, in an artery of
an animal to transmit pressure of fluid within that artery back to
pressure transducer 14 within housing 30. The sensed pressure is converted
to electrical signals by transmitter 16, and a telemetry signal is
transmitted to an external receiver (not shown).
Catheter 12 is a small diameter, hollow tube made of a biocompatible
material such as urethane. Patentcy of catheter 12 is maintained with very
low doses of a drug (in many cases a subsystemic dose). The drug (which is
an antithrombogenic solution) is supplied by implantable osmotic infusion
pump 18 through tube 20, check valve 24, and catheter 22 to proximal end
34 of catheter 12. In the preferred embodiment shown in the FIGURE, the
end of catheter 22 is welded in side-by-side relationship to nipple 32,
and proximal end 34 of catheter 12 slips over and is connected to both
catheter 22 and nipple 32.
The ability to maintain catheter patentcy at low doses of antithrombogenics
is due to a very low system compliance for device 10 which prevents blood
from entering catheter 12 in the presence of fluctuating pressures. In
addition, film coating 38 (shown as cross-hatched in the FIGURE) is formed
on the distal end 36 of catheter 12. Film coating 38, which is preferably
a urethane coating, provides a smooth surface which reduces the ability of
thrombi to adhere to catheter 12 in the presence of arterial blood flow.
In addition, coating 38 rounds over the distal end of catheter 36, and
provides a flow profile which reduces the presence of eddy currents at the
distal tip of catheter 12. The stable interface of heparinized saline (or
other antithrombogenic drug) exiting the lumen of catheter 12 at distal
end 36 provides a constant diffusion of the drug at the distal tip, where
it is most needed.
Low system compliance is achieved by the use of catheter materials for
catheters 12, 20 and 22 and dimensions of those catheters which provide
the least compliance consistent with their intended purpose. For example,
in a preferred embodiment of the present invention, catheter 12 is a
urethane tube having approximately a 0.7 mm outside diameter and a 0.2 mm
wall thickness. The use of urethane tubing, rather than more compliant
silicon tubing, for example, together with the relatively thick wall
minimizes compliance consistent with the need of catheter 12 to be
inserted into an artery of a small animal such as a rat.
Catheters 20 and 22 do not require the same flexibility, because they are
not inserted into an artery. In a preferred embodiment, catheters 20 and
22 are polyethylene or polyvinyl chloride tubes.
Flow restrictor 28, which in one embodiment is a 75 micron inside diameter
glass-inside-stainless steel tube, reduces the compliance of osmotic
fusion pump 18. This prevents blood from entering distal tip 36 of
catheter 12 during diastole.
In addition, check valve 24 is connected in the flow path from osmotic
infusion pump 18 to catheter 12. The purpose of check valve 24 is to
prevent blood from entering catheter 12 due to pump 18 compliance when the
mean blood pressure of the animal increases significantly.
Access catheter 26 is connected to catheter 20 in parallel with the outlet
of infusion pump 18. Access catheter 26 extends out of the animal's body.
Prior to placement of pump 18 within the animal's body, and prior to pump
18 reaching a satisfactory low level following implantation, fluid flow is
provided from an external infusion pump (not shown) through access
catheter 26, catheter 20, check valve 24, and catheter 22 to catheter 12.
After osmotic infusion pump 18 is operating, catheter access 26 can be
closed by simply sticking a pin (not shown) in its outer end, which keeps
fluid from leaking out of access catheter 26. By removing the pin and
connecting an external pressure transducer to access catheter 26, a
technician can monitor the pressure being sensed by catheter 12 and thus
verify that pressure transducer 14 and transmitter 16 are operating
properly. In addition, in the event that catheter 12 becomes blocked for
some reason, access catheter 26 can be used to supply fluid at a pressure
sufficient to flush out catheter 12, thus returning it to patentcy.
Device 10 of the present invention has been successfully used to monitor
blood pressure in small animals such as rats by implanting all of device
10 within the body of the animal, except for the outer end of access
catheter 26. In preferred embodiments, housing 30 is implanted and secured
within the peritoneal cavity; distal end 36 of catheter 12 is placed in
the descending aorta by inserting catheter 12 through the wall in the
artery and fixing in place with either silk suture or tissue adhesive; and
pump 18 (which is preferably an Alza osmotic infusion pump) is implanted
above the neck of the animal. The placement of pump 18 provides reasonable
access to permit replacement of the pump 18 as necessary.
In summary, the present invention offers significant advantages over prior
art techniques for monitoring pressure in laboratory animals. With the
present invention, pressure transducer 14 is placed remote from the
vessel, with pressure being transmitted to transducer 14 through a
fluid-filled catheter 12. This allows the capability of measuring pressure
within a very small vessel with excellent long term stability because it
allows the use of stable, commercially available sensors which cannot be
packaged in a size which could allow direct insertion into the vessel of a
small animal. Since the device also incorporates a means of reducing
fibrous growth on the catheter, it is possible to reduce or eliminate the
contribution of fibrotic growth to measurement instability. In addition,
the use of implantable osmotic infusion pump 18 allows an antithrombogenic
drug to be dispensed through the lumen of catheter 12 to maintain catheter
patentcy. The use of osmotic infusion pump 18 allows nearly all of device
10 to be enclosed within the body of the animal.
Device 10 of the present invention (combined with a radiotelemetry receiver
and computerized data collecting system) makes it is possible to automate
the process of collection of pressure data from laboratory animals. This
provides better quality and more frequent data while reducing the cost of
implementing many experimental protocals. The present invention allows the
animals to move freely within their cages, which not only reduces stress
caused by tethers, but also provides a more humane treatment of the
animal.
The device 10 of the present invention also is applicable to sensing
internal body pressure in humans, including blood pressure, interplural
pressure, intracranial pressure, and pressures within the gastointestinal
system. Such information can be used for diagnostic purposes, or as
feedback for closed loop control of infusion pumps capable of
administering pharmaceutical agents.
Although the present invention has been described with reference to
preferred embodiments, workers skilled in the art will recognize that
changes may be made in form and detail without departing from the spirit
and scope of the invention.
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