JP2015223421A - Nerve stimulation device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a nerve stimulation device capable of reducing occurrences of tachycardia even when pacing is induced, for example, by stimulating myocardial cells.SOLUTION: A nerve stimulation device 1A stimulates a nerve from inside a blood vessel, and includes a stimulation electrode 34 for applying electric stimulation through an inner wall of the blood vessel, and a control part for controlling a current or a voltage to be supplied to the stimulation electrode 34. The control part has, patterns for controlling the current or voltage, a first stimulation pattern of successively applying first stimulation waveforms repeated with a frequency greater than or equal to a frequency corresponding to an allowable maximum heart rate, and a second stimulation pattern of intermittently applying second stimulation waveforms repeated with a frequency less than or equal to the frequency corresponding to the allowable maximum heart rate.

Description

  The present invention relates to a nerve stimulation apparatus that is a therapeutic device that stimulates nerves transvascularly.

Conventionally, a nerve stimulation device configured to stimulate a nerve trunk through a blood vessel has been proposed. For example, Patent Document 1 discloses a method for selectively applying a nerve stimulus to a first nerve stimulation site of the heart, which is connected to the first channel in order to selectively apply the nerve stimulation to the first nerve stimulation site of the heart. An implantable medical device is described comprising a neurostimulator connected to the second channel.
In the device described in Patent Document 1, the first nerve stimulation site of the heart includes SVC-AO cardiac adipose tissue located proximal to the junction between the superior vena cava and the aorta, and the second nerve of the heart The stimulation site is associated with the sinoatrial (SA) node, PV cardiac adipose tissue located proximal to the junction between the right atrium and the right pulmonary vein, and the atrioventricular (AV) node, the inferior vena cava It is described to be selected from the group of adipose tissue consisting of IVC-LA cardiac adipose tissue located proximal to the junction between the left atrium and the left atrium.

Special table 2008-532630 gazette

However, the conventional nerve stimulation apparatus as described above has the following problems.
In US Pat. No. 6,057,059, “Some embodiments have a threshold for myocardial tissue depolarization (especially myelinated vagus nerve fibers of the parasympathetic nervous system) that is much smaller than myocardial tissue threshold. Electrical stimulation of autonomic nerves that innervate the myocardium without directly inducing contraction, with various stimulation frequencies following the ganglion nerve fibers (or, in the case of vagus nerve stimulation, nerve fibers before the ganglion) Can be used to depolarize ".
As described above, the threshold value of nerve depolarization is smaller than the threshold value of the myocardial tissue because, in Patent Document 1, the nerve stimulation site includes cardiac adipose tissue, whereby the stimulation energy is attenuated and transmitted to the cardiomyocytes. It is.
However, when nerve stimulation is performed through the superior vena cava and inferior vena cava close to the atria, it is known that cardiomyocytes are present in the superior vena cava and inferior vena cava.
Therefore, when nerve stimulation is performed from the superior vena cava or the inferior vena cava, an electrical signal for nerve stimulation is transmitted to the myocardial cells through the vascular endothelium, which is a very thin tissue, so that the myocardial cells are easily excited. When cardiomyocytes are excited, pacing is induced, which may adversely affect the treatment of patients with heart disease.

  The present invention has been made in view of the above problems, and provides a nerve stimulation device that can suppress the occurrence of a tachycardia state even when pacing is induced by stimulating cardiomyocytes or the like. With the goal.

  In order to solve the above problems, a nerve stimulation apparatus according to the first aspect of the present invention is a nerve stimulation apparatus that stimulates nerves from within a blood vessel, and includes a stimulation electrode for applying electrical stimulation through the inner wall of the blood vessel, A control unit that controls a current or voltage supplied to the stimulation electrode, and the control unit repeats at a frequency equal to or higher than a frequency corresponding to an allowable upper limit heart rate as the control pattern of the current or voltage. A configuration comprising: a first stimulation pattern that continuously applies a stimulation waveform; and a second stimulation pattern that intermittently applies a second stimulation waveform that is repeated at a frequency equal to or lower than a frequency corresponding to the allowable upper limit heart rate. And

  In the above nerve stimulation apparatus, it is preferable that the frequency in the second stimulation waveform is 2 Hz to 2.5 Hz.

  The nerve stimulation apparatus includes an electrocardiogram signal detection unit that detects a heart rate of a patient to be stimulated, and the control unit has a frequency equal to or lower than a frequency corresponding to the allowable upper limit heart rate in the second stimulation waveform. It is preferable to set according to the heart rate of the patient detected by the electrocardiogram signal detection unit.

  A nerve stimulation apparatus according to a second aspect of the present invention is a nerve stimulation apparatus that stimulates nerves from within a blood vessel, and includes a stimulation electrode for applying electrical stimulation through the inner wall of the blood vessel, and an electrocardiographic signal of a patient to be stimulated. An electrocardiogram signal detection unit to detect, an atrial refractory period prediction unit that predicts the timing of an atrial refractory period based on the electrocardiogram signal of the patient detected by the electrocardiogram signal detection unit, and a current supplied to the stimulation electrode Or a control unit that controls the voltage, and the control unit continuously applies a first stimulation waveform repeated at a frequency equal to or higher than the frequency corresponding to the allowable upper limit heart rate as the current or voltage control pattern. And a second stimulation pattern for applying a second stimulation waveform for performing electrical stimulation at the timing of the atrial refractory period predicted by the atrial refractory period prediction unit. .

  Since the nerve stimulation apparatus of the present invention can apply electrical stimulation by applying a stimulation waveform that does not become tachycardia even when the atrium is paced, even if pacing is induced by stimulating myocardial cells, etc. There exists an effect that generation | occurrence | production of a state can be suppressed.

It is a typical block diagram which shows the structure of the nerve stimulation apparatus of the 1st Embodiment of this invention. It is the typical partial enlarged view of the D section in FIG. 1, and its EE sectional drawing. It is a functional block diagram of the nerve stimulation apparatus of the 1st Embodiment of this invention. It is the typical graph which shows the 1st stimulation pattern of the nerve stimulation apparatus of the 1st Embodiment of this invention, and the elements on larger scale of the F section. It is the typical graph which shows the 2nd stimulation pattern of the nerve stimulation apparatus of the 1st Embodiment of this invention, and the elements on larger scale of the G section. It is the schematic diagram explaining the position of the opening formed in a patient, and the schematic diagram explaining the state which introduce | transduced the electrode part of the nerve stimulation apparatus of the 1st Embodiment of this invention into the blood vessel. It is a functional block diagram of the nerve stimulation apparatus of the 2nd Embodiment of this invention. It is a schematic diagram which shows an example of an electrocardiogram signal. It is a timing chart which shows the operation | movement at the time of the treatment of the nerve stimulation apparatus of the 2nd Embodiment of this invention. It is a functional block diagram of the nerve stimulation apparatus of the 3rd Embodiment of this invention. It is a typical graph which shows an example of the electrocardiogram signal and nerve stimulation pattern which show the operation | movement at the time of the treatment of the nerve stimulation apparatus of the 3rd Embodiment of this invention.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. In all the drawings, even if the embodiments are different, the same or corresponding members are denoted by the same reference numerals, and common description is omitted.

[First Embodiment]
A nerve stimulation apparatus according to a first embodiment of the present invention will be described.
FIG. 1 is a schematic configuration diagram showing the configuration of the nerve stimulation apparatus according to the first embodiment of the present invention. FIG. 2A is a schematic partial enlarged view of a portion D in FIG. FIG.2 (b) is EE sectional drawing in Fig.2 (a). FIG. 3 is a functional block diagram of the nerve stimulation apparatus according to the first embodiment of the present invention. FIG. 4A is a schematic graph showing a first stimulation pattern of the nerve stimulation apparatus according to the first embodiment of the present invention. FIG. 4B is a partially enlarged view of a portion F in FIG. FIG. 5A is a schematic graph showing a second stimulation pattern of the nerve stimulation apparatus according to the first embodiment of the present invention. FIG.5 (b) is the elements on larger scale of the G section in Fig.5 (a).
In the graphs of FIGS. 4A, 4B, 5A, and 5B, the horizontal axis represents time, and the vertical axis represents current.

A nerve stimulation apparatus 1A of the present embodiment shown in FIG. 1 is for indwelling in a patient's blood vessel for a certain period and applying electrical stimulation to surrounding nerve tissue through the vessel wall of the blood vessel. The nerve stimulation apparatus 1A is suitable for performing short-term nerve stimulation unlike a long-term nerve stimulation apparatus in which the entire system is implanted in the body.
The nerve stimulation apparatus 1 </ b> A includes an electrode unit 2 and an apparatus body 20 </ b> A that can be attached to and detached from the electrode unit 2.

  The electrode unit 2 includes a distal end fastener 31 and a proximal end fastener 32 that are spaced apart from each other, four wire portions 33 each having an end connected to the distal end fastener 31 and the proximal end fastener 32, and It has a pair of stimulation electrodes 34 provided on one of the four wire portions 33 and a wiring portion 35 whose tip is electrically connected to the stimulation electrode 34.

The distal end fastener 31 and the proximal end fastener 32 are formed in a substantially cylindrical shape with a material having biocompatibility such as stainless steel and titanium, for example. The distal end fastener 31 is disposed on the distal end side with respect to the proximal end fastener 32.
As shown in FIGS. 2A and 2B, the wire portion 33 includes a wire 41 (see FIG. 2B) provided at the center and an inner coating 42 (FIG. 2 (FIG. 2B) covering the outer peripheral surface of the wire 41. b)) and an outer coating 43 covering the outer peripheral surface of the inner coating 42.
The wire 41 is plastically deformed when an external force is applied to the wire 41 in a natural state where an external force other than gravity is not applied, such as a shape memory alloy or a super elastic wire, and then the external force is released. A material that returns to its original shape without any problems can be preferably used. The outer diameter of the wire 41 is set to, for example, 0.3 mm to 0.5 mm.
The inner coating 42 and the outer coating 43 are made of a resin such as polyurethane, for example. The inner coating 42 and the outer coating 43 are formed to have a thickness of 50 μm to 500 μm. By comprising in this way, the outer peripheral surface of the external film 43 becomes smooth, and it is prevented that a thrombus arises on this outer peripheral surface.

When the external coating 43 in one of the wire portions 33 of the electrode unit 2 is defined with a linear axis C1 (see FIG. 1) passing through the distal end fastener 31 and the proximal end fastener 32, FIG. As shown in b), a pair of through holes 43a are formed side by side in the direction of the axis C1 on the side opposite to the axis C1 in the middle portion in the direction of the axis C1.
The through-hole 43a is formed in a substantially elliptical shape or an oval shape that is long in the direction of the axis C1 (see FIG. 2A).

As shown in FIG. 2B, the cylindrical stimulation electrode 34 is provided between the inner coating 42 and the outer coating 43 on the back side of each through hole 43 a. The stimulation electrode 34 has an outer diameter equal to the inner diameter of the outer coating 43 and an axial length slightly longer than the through-hole 43a. The stimulation electrode 34 is made of, for example, a metal having biocompatibility such as a platinum iridium alloy.
Therefore, the inner coating 42 is inserted into each stimulation electrode 34, and the outer peripheral surface of the stimulation electrode 34 closes the through hole 43a, so that a portion overlapping the through hole 43a is exposed to the outside.
Electric wirings 35 a constituting the wiring part 35 are electrically connected to the inner peripheral surface of each stimulation electrode 34. As the electrical wiring 35a, for example, a stranded wire made of a nickel cobalt alloy (35NLT25% Ag material) having bending resistance is covered with an electrical insulating material (for example, ETFE (polytetrafluoroethylene) having a thickness of 20 μm). What was done can be used suitably.
The electrical wiring 35 a is arranged in the outer coating 43 and extends along the outer coating 43, and further extends to the proximal side through the proximal end fastener 32.

The wire portion 33 having such a configuration is a member having elasticity as a whole, and as shown in FIG. 1, all of the wire portions 33 are formed in a circular arc shape having a central angle of about 180 °. The radius of curvature of the wire portion 33 is set to about 10 mm to 20 mm, for example, according to the inner diameter of the indwelling blood vessel.
In the present embodiment, the four wire portions 33 are arranged at equal angles of 90 ° around the axis C1. That is, the wire portion 33 is arranged such that an intermediate portion in the direction of the axis C1 is curved so as to be separated from the axis C1, and the intermediate portions are separated from each other around the axis C1. For this reason, the four wire parts 33 are arrange | positioned on the spherical surface.

The four wire portions 33, the distal end fastener 31, and the proximal end fastener 32 constitute an electrode portion 38.
In the present embodiment, the outer diameter of the electrode portion 38 in the natural state is about 20 mm to 40 mm. This outer diameter is set larger than the inner diameter of the blood vessel in which the electrode part 38 is placed.
The wire portion 33 is joined to the distal end fastener 31 and the proximal end fastener 32 by welding, adhesion, caulking, or the like.

A distal end portion of a tubular lead body 45 is attached to the proximal end fastener 32. The lead main body 45 is made of, for example, polyurethane, and has an outer diameter of 2 mm to 3 mm and a length of about 500 mm, for example. The aforementioned wiring part 35 is inserted into the lead main body 45.
For example, a known IS1-type connector 48 is provided at the base end portion of the lead body 45, and the base end portion of the wiring portion 35 is electrically connected to the connector 48.
The connector 48 includes a negative electrode connector pin 48a and a positive electrode connector pin 48b, and a pair of rubber rings 48c.
The rubber ring 48c insulates the negative electrode connector pin 48a and the positive electrode connector pin 48b from each other and keeps the watertight when connected to the apparatus main body 20A.
Both the negative electrode connector pin 48a and the positive electrode connector pin 48b are made of stainless steel. The rubber ring 48c is made of silicone rubber having biocompatibility.
As the connector 48, in addition to the IS1 type, a waterproof connector used when the apparatus main body 20A is installed outside the body can be used.

The apparatus main body 20A is an apparatus part that generates electric stimulation by supplying electric power to the stimulation electrode 34 based on the operation of the operator when the electrode unit 38 is placed in the blood vessel.
As shown in FIG. 1, the apparatus main body 20 </ b> A is provided with a connector 21 for attaching and detaching a connector 48, whereby the base end portion of the wiring portion 35 is detachable. When the connectors 21 and 48 are connected, the apparatus main body 20A can apply a signal waveform for generating electrical stimulation between the pair of stimulation electrodes 34 provided on the respective wire portions 33. . At that time, one stimulation electrode 34 of the pair of stimulation electrodes 34 acts as a plus side electrode, and the other stimulation electrode 34 acts as a minus side electrode.

  The functional configuration of the apparatus main body 20A includes a pulse generator 100A and a controller 101A as shown in FIG.

The pulse generator 100A is electrically connected to the stimulation electrode 34 via the connector 48, and applies electrical stimulation to the inner wall of the blood vessel via the stimulation electrode 34. Therefore, the pulse generator 100A has a stimulation waveform by a constant current method or a constant voltage method. It is an apparatus part which consists of a power supply which outputs a pulse-like signal waveform.
The pulse generation unit 100A is electrically connected to the control unit 101A, and outputs a pulsed signal waveform corresponding to the information of the stimulation pattern from the control unit 101A.

The control unit 101A is a device part that controls the pattern, amplitude, and generation timing of the signal waveform applied to the pulse generation unit 100A, and is electrically connected to the pulse generation unit 100A.
Further, the control unit 101A is communicably connected with an operation unit 22 for selecting a control mode of the control unit 101A and inputting necessary control information to the control unit 101A in advance.
The operation unit 22 may be an operation input means such as a switch, a touch panel, or a keyboard attached to the apparatus main body 20A. For example, an external device such as an electrocardiogram signal detection device attached to a patient is connected via an appropriate communication line. The operation may be performed by a control signal from the external device.

The control unit 101A has a search mode and a nerve stimulation mode as main control modes, and these can be switched and executed by an operation input from the operation unit 22.
The search mode is a control mode in which a stimulus pattern (hereinafter referred to as a search stimulus pattern) for searching for an appropriate arrangement position of the electrode unit 38 is applied.
The nerve stimulation mode is a control mode in which a stimulation pattern (hereinafter referred to as a nerve stimulation pattern) that stimulates a nerve to be stimulated to treat a patient is applied.

The search stimulus pattern has a constant repetition frequency f _S1 (FIG. 4B) as schematically shown in FIGS. 4A and 4B as a waveform 200 (first stimulus waveform, first stimulus pattern). A biphasic waveform with a two-phase rectangular wave having a reference) is a continuous pattern that continues without being interrupted until the generation is stopped. 4A and 4B show signal waveforms of a constant current method as an example (the same applies to the following).
In the search mode, it is necessary to quickly and accurately find an appropriate arrangement position of the stimulation electrode 34. For this reason, it is preferable that a search stimulus pattern is a pattern which can observe a large heartbeat fall with a response time as short as possible.
Specifically, the repetition start frequency f _S1 is set to a considerably higher frequency than the frequency corresponding to the standard heart rate. For example, the repetition frequency f _S1 is preferably 10 Hz to 50 Hz. Within such a range, the response time of heartbeat reduction, which is a vagus nerve stimulation response that governs the heart, is as fast as several seconds, and the heartbeat reduction width increases.

The degree of heart rate reduction is preferably 5% to 10%. Even if the blood pressure decreases due to sudden heartbeat reduction, when the nerve stimulation apparatus 1A is used in the search mode, an appropriate countermeasure can be taken because the doctor is monitoring.
The amplitude A and the pulse width T _P1 (see FIG. 4B), which are the stimulation intensities of the search stimulation pattern, can be appropriately set based on the energy amount for causing a preferable heartbeat reduction.
The amplitude A is preferably 1 mA or more and 20 mA, for example.
The pulse width _{T P1,} for example, 0.1Msec～0.4Msec are preferred.

The nerve stimulation pattern is a bi-phase rectangular wave having a constant repetition frequency f _S2 (see FIG. 5B) as schematically shown as a waveform 201 (second stimulation pattern) in FIG. The waveform group W (second stimulation waveform) in which the phasic waveform continues continuously for the time T1 is a pattern that is intermittently repeated until the generation is stopped. The pause time T2 between the waveform groups W is set longer than the time T1.
Specifically, for example, it is possible to set values such as T1 = 10 (sec) and T2 = 50 (sec).

  In a conventional nerve stimulation apparatus, a nerve stimulation pattern that has a repetition frequency similar to that of the search stimulation pattern and intermittently applies a group of waveforms, the amplitude of which is adjusted as necessary, with a pause time in between is used. . In this case, stimulation can be performed without causing a rapid heartbeat reduction during search, but in the unlikely event that the stimulation electrode is misaligned due to prolonged use or the influence of patient movement, If the stimulation electrode contacts the atrium or stimulates the myocardial cells in the superior vena cava, there is a risk of pacing the atrium.

Therefore, the nerve stimulation pattern in the present embodiment has a repetition frequency so that even if the stimulation electrode 34 abuts the atrium or stimulates the myocardial cells to pace the atrium, an unacceptable tachycardia state does not occur. f _S2 is selected from the range below the frequency corresponding to the allowable upper limit heart rate.
Although the allowable upper limit heart rate varies depending on the age and medical condition of the patient, the upper limit value of the repetition frequency f _S2 is preferably selected from the range of 2 Hz to 2.5 Hz because it is generally 100 bpm to 150 bpm.
If the repetition frequency f _S2 is too low, the amount of energy necessary for stimulation cannot be applied, so the lower limit value of the repetition frequency f _S2 is preferably 0.83 Hz.
A more preferable range of the repetition frequency f _S2 is a frequency corresponding to the range of the normal heart rate of the patient.

The amplitude B, which is the stimulation intensity of the nerve stimulation pattern, and the pulse width T _P2 (see FIG. 5B) are energy amounts that give necessary stimulation to the nerve to be stimulated according to the repetition frequency f _S2 and the time T1. Based on this, it can be set appropriately. For example, even if the amplitude B is about the same as the amplitude of the prior art, the pulse width _TP2 can be widened and set to the same amount of energy.
The amplitude B is preferably 1 mA or more and 20 mA, for example.
The pulse width _{T P1,} for example, 0.01Msec～20msec are preferred.
For example, the time T1 during which the waveform group W is applied and the pause time T2 are set to 10 sec and 50 sec, respectively, and in the conventional technique, stimulation is performed under conditions such that the repetition frequency is 20 Hz, the amplitude is 5 mA, and the pulse width is 0.1 msec. Suppose that In order to perform electrical stimulation with an energy amount equivalent to this, conditions such as f _S2 = 1 (Hz), B = 5 (mA), and T _P2 = 2 (msec) may be used.

  In the apparatus main body 20A, the apparatus configurations of the pulse generation unit 100A and the control unit 101A may be configured only by hardware, or may include appropriate hardware, a CPU, a memory, an input / output interface, an external storage device, and the like. You may implement | achieve by the combination with a computer.

Next, a technique for placing the electrode portion 38 of the electrode unit 2 in the superior vena cava using the nerve stimulation apparatus 1A configured as described above will be described together with the operation of the nerve stimulation apparatus 1A. In this case, the outer diameter of the electrode portion 38 in the natural state is set larger than the inner diameter of the superior vena cava. The nerve stimulation apparatus 1A described below is not equipped with the apparatus main body 20A as an initial state.
Fig.6 (a) is a schematic diagram explaining the position of the opening formed in a patient. FIG. 6B is a schematic diagram showing a state in which the nerve stimulation apparatus according to the first embodiment of the present invention is placed in the superior vena cava.

First, as shown in FIG. 6A, the surgeon incises the vicinity of the neck of the patient P to form an opening P1.
A known introducer or dilator (not shown) is attached to the opening P1, and the electrode unit 2 is introduced from the electrode portion 38 side. At this time, it introduces, confirming the position of the electrode unit 2 by confirming the position of the wire 41 of the wire part 33 or the wiring part 35 under X-ray | X_line.
When the electrode part 38 is introduced into the external jugular vein P2, each wire part 33 is elastically deformed toward the axis C1 side and is reduced in diameter as a whole by being pushed by the inner wall of the external jugular vein P2. It extends in the direction of the axis C1. Thereby, the outer diameter of the electrode part 38 becomes smaller than the outer diameter in a natural state.

The operator introduces the electrode unit 2 while confirming the position under the X-ray, and roughly arranges the electrode unit 38 in the superior vena cava P3 (blood vessel) as shown in FIG. 6B. Also at this time, since the outer diameter of the electrode portion 38 is set as described above, each wire portion 33 is pressed against the axis C1 side by the superior vena cava P3. Accordingly, although not shown in FIG. 6B, the respective stimulation electrodes 34 exposed from the through holes 43a are arranged so as to face the inner wall of the superior vena cava P3.
A vagus nerve P6 (nerve) is running adjacent to the superior vena cava P3.

Subsequently, outside the body of the patient P, the connector 48 of the wiring part 35 and the connector 21 of the apparatus main body 20A are connected.
Next, the surgeon operates the operation unit 22 to set the control mode of the control unit 101A to the search mode.
As a result, the information on the search stimulus pattern is sent from the control unit 101A to the pulse generating unit 100A, and the waveform 200 as shown in FIGS. 4A and 4B is applied to the stimulation electrode 34 from the pulse generating unit 100A. The
The surgeon operates the lead body 45 to adjust the longitudinal position of the superior vena cava P3 in the electrode portion 38, and an electrocardiograph attached to the patient P while rotating the lead body 45 about the axis C1. To measure heart rate. The pair of stimulation electrodes 34 are arranged so as to approach and face the vagus nerve P6, and when the electrical stimulation transmitted from the pair of stimulation electrodes 34 to the vagus nerve P6 increases, the heart rate of the patient P decreases most. To do. The surgeon adjusts the direction of the electrode portion 38 around the axis C1 so that the heart rate decreases most, that is, the pair of stimulation electrodes 34 faces the vagus nerve P6.
When the adjustment of the orientation of the electrode unit 38 is completed, the search mode is terminated by operating the operation unit 22.
In this way, the position of the electrode portion 38 around the axis C1 is positioned, and the electrode unit 2 is placed in the superior vena cava P3.

In such a search mode, the operator performs a procedure while monitoring the heart rate, blood pressure, and the like with an electrocardiograph or the like.
For this reason, for example, even if a sudden heart rate drop occurs, the surgeon copes with placement.
In addition, the surgeon searches for an arrangement position where the heartbeat lowering occurs. For example, when the stimulation electrode 34 stimulates myocardial cells and signs of pacing of the atrium are observed, the stimulation electrode 34 is immediately moved to another position. Moved.

Next, an anticoagulant is delivered from the outside of the patient P and released into the blood of the blood vessel in which the electrode unit 2 is placed. The speed at which the anticoagulant is released is, for example, about 0.05 ml to 60 ml per hour, and the anticoagulant is continuously released while the electrode unit 38 is placed. The released anticoagulant moves along with the blood along the wire portion 33 toward the distal end fastener 31, and the blood is coagulated at the wire portion 33 and the fasteners 31 and 32 and thrombus formation is suppressed.
The timing for starting the supply of the anticoagulant is not limited to this, and can be set as appropriate, such as starting the supply of the anticoagulant when the electrode portion 38 is placed in the superior vena cava P3.
Further, the means for releasing the anticoagulant is not particularly limited. For example, a central venous catheter or an infusion line may be used. In addition, a liquid supply pipe that opens at the tip of the wiring part 35 is provided in the lead main body 45 along the wiring part 35, and a syringe piston pump or the like is provided on the liquid supply pipe on the proximal end side of the lead main body 45 that is outside the patient P. The anticoagulant may be injected by the method.

Next, the operation when nerve stimulation for treatment is performed after the electrode unit 2 is placed in this way will be described.
When an operation input for starting the nerve stimulation mode is performed from the operation unit 22, the control mode of the control unit 101A is set to the nerve stimulation mode.
The nerve stimulation mode may be started by the operation of the therapist, and when an external device is connected as the operation unit 22, for example, the nerve stimulation mode is detected by the external device detecting an abnormality of the patient. May start.
Moreover, it may be started immediately after the placement of the electrode unit 2 or may be started after a certain time after placement.

When the nerve stimulation mode is started, information on the nerve stimulation pattern is sent from the control unit 101A to the pulse generating unit 100A, and the pulse generating unit 100A sends the information to the stimulation electrode 34 as shown in FIGS. 5 (a) and 5 (b). A simple waveform 201 is applied.
As a result, electrical stimulation is applied to the vagus nerve P6 through the stimulation electrode 34. The application time is determined in advance according to the purpose of treatment.

At this time, immediately after the electrode unit 2 is placed, the arrangement position of the stimulation electrode 34 and the position of the vagus nerve P6 are not misaligned. However, if the time has elapsed after the placement, there is a possibility that the stimulation electrode 34 is displaced due to, for example, the influence of the patient's body movement.
For example, the atrium may be paced when the stimulation electrode 34 abuts the atrium or stimulates myocardial cells in the superior vena cava P3.
However, in the present embodiment, since the repetition frequency f _S2 of the waveform of the neural stimulation pattern is equal to or lower than the frequency corresponding to the allowable upper limit heart rate, even if the atrium is paced, the heart rate is equal to or lower than the allowable upper limit heart rate. An incapable tachycardia does not occur. For this reason, arrhythmias such as atrial fibrillation are not caused except in cases where arrhythmias caused by patients occur at the same time.

When it becomes unnecessary to place the electrode unit 2 for treatment, the apparatus main body 20A is removed, and the electrode unit 2 is pulled back. At this time, since the outer diameter of the electrode portion 38 changes according to the inner diameter of the blood vessel or the introducer, it can be removed from a small wound when inserted during placement, and the electrode unit 2 can be removed from the body of the patient P. It can be easily taken out. Surgical reoperation is not required for removal of the electrode unit 2.
Thereafter, appropriate procedures such as suturing the opening P1 are performed, and the procedure for removing the electrode unit 2 is completed.

  As described above, according to the nerve stimulation apparatus 1A of the present embodiment, even when the atrium is paced, it is possible to apply a nerve stimulation pattern having a stimulation waveform that does not become a tachycardia state and apply electrical stimulation. The occurrence of tachycardia can be suppressed even if pacing is induced by stimulation or the like.

[Second Embodiment]
Next, a nerve stimulation apparatus according to a second embodiment of the present invention will be described.
FIG. 7 is a functional block diagram of the nerve stimulation apparatus according to the second embodiment of the present invention. FIG. 8 is a schematic diagram showing an example of an electrocardiogram signal.

A nerve stimulation apparatus 1B of the present embodiment shown in FIG. 1 includes an apparatus body 20B instead of the apparatus body 20A of the nerve stimulation apparatus 1A of the first embodiment.
As illustrated in FIG. 7, the apparatus main body 20B includes a control unit 101B instead of the control unit 101A of the apparatus main body 20A of the first embodiment, and includes an electrocardiogram signal detection unit 102B and a storage unit 103B. Is.
Hereinafter, a description will be given centering on differences from the first embodiment.

The controller 101B controls the pattern, amplitude, and generation timing of the signal waveform applied to the pulse generator 100A, and sets the signal waveform according to the heart rate of the patient. It is the device part which controls.
The control unit 101B is communicably connected to the pulse generation unit 100A, the electrocardiogram signal detection unit 102B, the storage unit 103B, and the operation unit 22.
Similar to the control unit 101A of the first embodiment, the control unit 101B has a search mode and a nerve stimulation mode as main control modes, and switches between these by an operation input from the operation unit 22. Is possible.

The search mode is the same control mode as in the first embodiment.
As in the first embodiment, the nerve stimulation mode of the present embodiment is a waveform 205 (second stimulation pattern) made up of a biphasic waveform as shown in FIGS. 5A and 5B as a nerve stimulation pattern. ) Is applied to the pulse generator 100A. However, the repetition frequency f _S2 in the waveform group W is different from the first embodiment in that the repetition frequency f _S2 is changed according to the heart rate calculated by the electrocardiogram signal detection unit 102B.
Details of the control of the control unit 101B will be described together with the operation of the nerve stimulation apparatus 1B.

The electrocardiogram signal detection unit 102B is a device part that acquires a patient's electrocardiogram signal using the stimulation electrode 34 as a detection electrode and analyzes the acquired electrocardiogram signal.
A typical electrocardiogram signal has a waveform as shown in FIG. 8, and a P wave, a QRS wave, and a T wave are observed in this order.
The electrocardiogram signal detection unit 102B calculates the heart rate and the average heart rate during the measurement period by detecting the peak position of the R wave and measuring the RR interval, which is the interval between adjacent R waves.
The electrocardiogram signal detection unit 102B stores the calculated heart rate and average heart rate in the storage unit 103B.

Next, the operation of the nerve stimulation apparatus 1B of the present embodiment will be described focusing on the operation of the nerve stimulation mode different from the first embodiment.
FIG. 9 is a timing chart showing an operation during treatment of the nerve stimulation apparatus according to the second embodiment of the present invention.

In the same manner as in the first embodiment, after the electrode unit 2 is placed in the superior vena cava P3, when an operation input for starting the nerve stimulation mode is performed from the operation unit 22, the control mode of the control unit 101B is set to the nerve stimulation. Set to mode.
When the nerve stimulation mode is started, as shown in FIG. 9, a heartbeat detection period for performing a heartbeat detection operation for a time Td, and a stimulation permission period for performing nerve stimulation by a nerve stimulation pattern for a time Tst. They are alternately set in order. Specifically, timing signals as shown in FIG. 9 are generated, and each operation is permitted only while these timing signals are in the on state.

The time Td of the heartbeat detection period can be set to 1 min, for example.
The time Tst for the stimulation permission period can be appropriately set in consideration of the stability of the patient's heart rate. If the patient's heart rate is likely to change, it can be set short, and if it is stable, it can be set long. An example of the time Tst can be 10 min.

For example, when the heart rate detection period is started at time t0, the control unit 101B sends a control signal for starting detection of the electrocardiogram signal to the electrocardiogram signal detection unit 102B.
The electrocardiogram signal detection unit 102B starts acquiring an electrocardiogram signal using the stimulation electrode 34 to which no stimulation waveform is applied as a detection electrode because the timing signal for permitting the stimulus is off.
Then, the electrocardiogram signal detection unit 102B acquires the time when the R wave reaches a peak from the waveform change of the electrocardiogram signal, takes the difference between these times, and measures the RR interval.
The measured RR interval is converted into a heart rate by the electrocardiogram signal detection unit 102B, and sequentially stored in the storage unit 103B.

Thus, at time t1 when the time Td has elapsed, the heartbeat detection timing signal is turned off and the stimulus permission timing signal is turned on.
At time t1, the electrocardiogram signal detection unit 102B calculates an average heart rate from the heart rate measured at time Td and stores it in the storage unit 103B.
In addition, the control unit 101B monitors whether or not the average heart rate from time t0 to t1 is stored in the storage unit 103B, and acquires the stored average heart rate.

First, the control unit 101B determines whether the acquired average heart rate is not in a bradycardia state or a tachycardia state.
As the determination criterion, for example, whether the average heart rate is less than 50 bpm can be employed as the determination criterion for bradycardia, and whether the average heart rate exceeds 150 bpm can be employed as the determination criterion for tachycardia. Further, such a determination criterion can be individually set according to the pathology of a patient who uses the nerve stimulation apparatus 1B.

  When it is determined that the pulse is in a bradycardia state or a tachycardia state, the control unit 101B issues a warning notifying that the stimulation permission period ends and the heart rate is abnormal. For example, sound or light is emitted by a warning generation unit (not shown), or a warning message is displayed on a display unit (not shown).

When it is determined that neither the bradycardia state nor the tachycardia state is present, the control unit 101B converts the acquired average heart rate into a frequency, and sets this frequency as the repetition frequency f _S2 of the nerve stimulation pattern in the current stimulation permission period. To do.
The control unit 101B sends information on a nerve stimulation pattern defined by the repetition frequency f _S2 , the preset amplitude B, and the pulse width _TP2 to the pulse generation unit 100A. Thereby, the waveform 205 as schematically shown in FIGS. 9, 5A, and 5B is applied from the pulse generation unit 100A to the stimulation electrode 34.
In this way, electrical stimulation is applied to the vagus nerve P6 through the stimulation electrode 34 during the stimulation permission period.
For example, in the above specific example, the intermittent waveform cycle in which the stimulation waveform is applied for 10 seconds and paused for 50 seconds is repeated 10 times during the time Tst.

In the stimulation permission period from time t1 to time t2, a nerve stimulation pattern having a repetition frequency f _S2 based on the average heart rate of the patient actually measured in the immediately preceding heart rate detection period is applied, so the atrium is paced. However, since the heart rate is almost the same as the heart rate of the patient immediately before the start of stimulation, the tachycardia state does not occur. For this reason, it is difficult to cause arrhythmias such as atrial fibrillation.

During time t2 to t3, which is the next heartbeat detection period, the same heartbeat detection operation as described above is performed. In this case, the heart rate acquired by the electrocardiogram signal detection unit 102B is the heart rate immediately after receiving the stimulation of the neural stimulation pattern between time t1 and time t2, and the heart rate between time t0 and time t1. May change.
At time t3 to t4, which is the next stimulation permission period, except that a nerve stimulation pattern having a repetition frequency f _S2 corresponding to the average heart rate based on the heart rate acquired during time t2 to t3 is applied. The same operation as at times t1 to t2 is performed.

For this reason, if a change occurs in the heart rate of the patient at times t2 to t3, the stimulation is immediately stopped and a warning is issued if the heart rate is in a bradycardia state or tachycardia state.
In addition, when neither the bradycardia state nor the tachycardia state, nerve stimulation is performed according to the average heart rate in the latest heartbeat detection period.

Thus, according to the nerve stimulation apparatus 1B of the present embodiment, as in the first embodiment, electrical stimulation is performed by applying a nerve stimulation pattern having a stimulation waveform that does not enter a tachycardia state even when the atrium is paced. Therefore, even if pacing is induced by stimulating cardiomyocytes, the occurrence of tachycardia can be suppressed.
In the present embodiment, the repetition frequency f _S2 of the nerve stimulation pattern is changed corresponding to the change in the heart rate of the patient for each repetition period of heart rate detection. Therefore, immediately before pacing even if the atrium is paced. The heart rate is almost the same as that of the heart rate, and the change in heart rate can be more reliably suppressed.

[Third Embodiment]
Next, a nerve stimulation apparatus according to a third embodiment of the present invention will be described.
FIG. 10 is a functional block diagram of the nerve stimulation apparatus according to the third embodiment of the present invention.

A nerve stimulation apparatus 1C of the present embodiment shown in FIG. 1 includes an apparatus body 20C instead of the apparatus body 20A of the nerve stimulation apparatus 1A of the first embodiment.
As shown in FIG. 10, the apparatus main body 20C includes a control unit 101C instead of the control unit 101A of the apparatus main body 20A of the first embodiment, and includes a detection electrode 36, an electrocardiogram signal detection unit 102C, and a storage unit 103B. And an atrial refractory period prediction unit 104C.
Here, the storage unit 103B has the same configuration as that of the second embodiment.
The following description will focus on differences from the first and second embodiments.

The control unit 101C controls the pattern, amplitude, and generation timing of the signal waveform applied to the pulse generating unit 100A, and sets the signal waveform in accordance with the heart rate of the patient, and an atrial chamber described later. It is a device part that controls the operation of the refractory period prediction unit 104C.
The control unit 101C is communicably connected to the pulse generation unit 100A, the storage unit 103B, the atrial refractory period prediction unit 104C, and the operation unit 22.
Similar to the control unit 101A of the first embodiment, the control unit 101C has a search mode and a nerve stimulation mode as main control modes, which are switched by an operation input from the operation unit 22. Is possible.

The search mode is the same control mode as in the first embodiment.
In the nerve stimulation mode of the present embodiment, as in the first embodiment, a pulse group is generated as a nerve stimulation pattern within the range of the atrial refractory period ARP as the waveform group W of the biphasic waveform shown in FIG. Applied to the part 100A. At this time, the repetition frequency f _S2 , the amplitude B, and the pulse width _TP2 are set so that the energy amount of the pulse applied during the atrial refractory period ARP becomes an energy amount necessary for nerve stimulation.
The number of pulses in one atrial refractory period ARP is preferably 1 pulse to 10 pulses, more preferably several pulses.
As shown in FIG. 8, the atrial refractory period ARP exists in the region between the peak of the P wave and the peak of the Q wave, and is, for example, in the range of about 150 msec preceding the peak of the R wave. f _S2 is preferably 0.83 Hz to 2.5 Hz.
In this case, the amplitude B is preferably 1 mA or more and 20 mA, for example.
The pulse width _{T P2,} for example, 0.01Msec～1msec are preferred.
Details of the control of the control unit 101C will be described together with the operation of the nerve stimulation apparatus 1C.

The detection electrode 36 is an electrode for detecting a patient's electrocardiogram signal, and a bipolar electrode pair is disposed on the patient's body surface or inside the body.
When provided in the patient's body, it may be provided separately from the electrode portion 38 of the electrode unit 2, or may be provided on a wire portion 33 different from that provided with the stimulation electrode 34.
In the case where the detection electrode 36 is provided separately from the electrode portion 38, although not particularly illustrated, for example, one electrode can be provided for each of the distal end fastener 31 and the proximal end fastener 32.
Further, the lead body 45 can be provided on the outer peripheral portion at an appropriate position in the longitudinal direction.
Also, a configuration is possible in which a passage is provided in the lead main body 45, a catheter-like detection electrode is inserted into the passage, and the opening is provided in the distal end fastener 31 and is taken into and out of the blood vessel. In this case, it is possible to detect the electrocardiogram signal by inserting it into the atrium where the electrocardiogram signal intensity is strongest.
The detection electrode 36 is electrically connected to the electrocardiogram signal detection unit 102C, and can send an electrocardiogram signal to the electrocardiogram signal detection unit 102C.

The electrocardiogram signal detection unit 102 </ b> C is a device part that acquires the electrocardiogram signal of the patient sent from the detection electrode 36 and analyzes the acquired electrocardiogram signal.
In this embodiment, when the electrocardiogram signal detection unit 102C detects the peak value of the R wave, the heartbeat synchronization signal of the control unit 101C is transmitted at that timing.
Also, the electrocardiogram signal detection unit 102C calculates the RR interval from the electrocardiogram signal and sequentially stores it in the storage unit 103B.

The atrial refractory period prediction unit 104C is a device part that predicts the atrial refractory period based on the information calculated by the electrocardiogram signal detection unit 102C. In the present embodiment, based on the RR interval calculated by the electrocardiogram signal detection unit 102C and stored in the storage unit 103B, a prediction timing at which the next R wave appears is calculated, and a certain time preceding the prediction timing is calculated. The prediction is made as the refractory period, and the prediction result is sent to the control unit 101C as the application permission period of the neural stimulation pattern.
As the RR interval used for the prediction, the latest measured value may be used, an average value of a plurality of recent RR intervals may be used, or an approximate expression may be applied to changes in the recent RR intervals. The next RR interval may be estimated by fitting.
The predetermined time to be predicted as the atrial refractory period ARP may be appropriately determined from, for example, average atrial refractory period data, or the atrial refractory period ARP of the patient to be stimulated may be determined from previously measured data. Also good.
In this embodiment, a time width of 150 msec preceding the R wave prediction timing is predicted as an atrial refractory period ARP.

Next, the operation of the nerve stimulation apparatus 1C of the present embodiment will be described focusing on the operation of the nerve stimulation mode different from the first embodiment.
FIGS. 11A and 11B are schematic graphs showing an example of an electrocardiogram signal and a nerve stimulation pattern showing an operation at the time of treatment of the nerve stimulation apparatus according to the third embodiment of the present invention. The horizontal axis represents the time when the scales are adjusted, and the vertical axis represents the signal value of the electrocardiogram signal and FIG. 11 (b) represents the current.

In the same manner as in the first embodiment, after the electrode unit 2 is placed in the superior vena cava P3, when an operation input for starting the nerve stimulation mode is performed from the operation unit 22, the control mode of the control unit 101C is set to the nerve stimulation. Set to mode.
When the nerve stimulation mode is started, the control unit 101C sends a control signal for starting detection of an electrocardiogram signal to the electrocardiogram signal detection unit 102B.
As a result, the electrocardiogram signal detection unit 102C acquires an electrocardiogram signal from the detection electrode 36, and an electrocardiogram signal 206 as shown in FIG. 11A is acquired.
When the electrocardiogram signal 206 is transmitted from the detection electrode 36, the electrocardiogram signal detection unit 102C detects the time when the peak of the R wave is reached from the waveform change of the electrocardiogram signal 206, and outputs a heartbeat synchronization signal to the control unit 101C. While sending out, the difference with the peak time of the R wave detected most recently is taken, and it memorize | stores in the memory | storage part 103B as data of an RR space | interval.
When one or more data of such RR intervals are calculated, the next timing at which the R wave is generated is predicted based on the RR intervals. For example, the R-R interval obtained by time t0, when the time the next R wave is generated is predicted that after _{T R1,} the time width of the atrial refractory period ARP as _T ARP -150 (msec), nerve The stimulation pattern application start timing tst1 is calculated by the following equation (1) and sent to the control unit 101C.

tst1 = T _R1 −T _ARP (1)

Upon receiving the application start time tst1, the control unit 101C receives information on the preset nerve stimulation pattern after the tst1 from the reception of the latest heartbeat synchronization signal as shown in FIG. 11 (b). To send.
Thereby, a waveform 207 (second stimulation waveform, second stimulation pattern) of about several pulses is applied to the stimulation electrode 34 from the pulse generation unit 100A within the atrial refractory period ARP.
At this time, the repetition frequency f _S2 of the waveform 207 is higher than the frequency corresponding to the heart rate of the patient, but since it is applied within the atrial refractory period ARP, the atrium is not paced and a tachycardia condition does not occur. For this reason, arrhythmias such as atrial fibrillation are not caused except in cases where arrhythmias caused by patients occur at the same time.

Similarly, when the next R wave peak is detected at time t1 by the electrocardiogram signal detection unit 102C, a heartbeat synchronization signal is transmitted to the control unit 101C, and t1-t0 which is the most recent RR interval. Is calculated and stored in the storage unit 103B. Then, based on the stored information, the time the next R-wave occurs predicts that T _R2, the application start timing tst2 the next nerve stimulation pattern is calculated by the following equation (2), the control unit 101C Send it out.

tst2 = T _R2 −T _ARP (2)

  By repeating such an operation, the nerve stimulation pattern is intermittently applied only at the timing within the atrial refractory period ARP, and the nerve stimulation is performed.

Thus, according to the nerve stimulation apparatus 1C of the present embodiment, as in the first embodiment, electrical stimulation is performed by applying a nerve stimulation pattern having a stimulation waveform that does not enter a tachycardia state even when the atrium is paced. Can be given.
In this embodiment, since the neural stimulation pattern is applied only to the atrial refractory period ARP based on the measurement of the electrocardiogram signal, it does not induce atrial pacing, and thus more reliably suppress the occurrence of a tachycardia state. Can do.

  In the description of each of the above embodiments, the example in which the stimulation electrode is arranged in the superior vena cava to stimulate the vagus nerve is described as an example, and the stimulation electrode stimulates nerves other than the vagus nerve. You may do. In this case, the stimulation electrode can be disposed in an appropriate blood vessel that can transmit the stimulation to the nerve that performs the stimulation.

  In the description of the second and third embodiments, the example in which the electrocardiogram signal detection units 102B and 102C are built in the apparatus main bodies 20B and 20C has been described. However, the electrocardiogram signal detection units 102B and 102C , May be provided outside the apparatus main bodies 20B and 20C.

  In the description of the third embodiment, the example in which the atrial refractory period is predicted from the RR interval has been described. However, the electrocardiogram signal detection unit 102C directly determines the position of the atrial wave from the electrocardiogram signal. It may be detected to predict an atrial refractory period. In this case, it is possible to accurately predict the atrial refractory period by measuring information such as amplitude (intensity) and width (time) in the patient's atrial wave in advance and storing it in the storage unit 103B. .

  Further, in the description of each of the above embodiments, the frequency corresponding to the heart rate has been described as being converted by the control unit as an example. However, the conversion is not limited, for example, the conversion is performed by the electrocardiogram signal detection unit. Also good.

  Further, all the components described above can be implemented by being appropriately combined or deleted within the scope of the technical idea of the present invention.

1A, 1B, 1C Neural stimulation device 2 Electrode unit 20A, 20B, 20C Device main body 34 Stimulation electrode 36 Detection electrode 38 Electrode unit 45 Lead main body 100A Pulse generation unit 101A, 101B, 101C Control unit 102B, 102C Electrocardiogram signal detection unit 103B Storage unit 104C Atrial refractory period prediction unit 200 waveform (first stimulus waveform, first stimulus pattern)
201, 205 waveform (second stimulus pattern)
207 waveform (second stimulus waveform, second stimulus pattern)
206 ECG signal ARP Atrial refractory period C1 axis f _S1 repetition frequency (frequency corresponding to heart rate above allowable upper limit heart rate)
f _S2 repetition frequency (frequency corresponding to heart rate below allowable upper limit heart rate)
P Patient P3 Superior vena cava (blood vessel)
P6 Vagus nerve (nerve)
W waveform group (second stimulus waveform)

Claims (4)

A nerve stimulation device for stimulating nerves from inside a blood vessel,
A stimulation electrode for applying electrical stimulation through the inner wall of the blood vessel;
A control unit for controlling the current or voltage supplied to the stimulation electrode,
The control unit, as the current or voltage control pattern,
A first stimulation pattern for continuously applying a first stimulation waveform repeated at a frequency equal to or higher than a frequency corresponding to the allowable upper limit heart rate;
A second stimulation pattern for intermittently applying a second stimulation waveform repeated at a frequency equal to or lower than the frequency corresponding to the allowable upper limit heart rate;
Having
Neural stimulator. The frequency in the second stimulus waveform is:
The nerve stimulation apparatus according to claim 1, wherein the nerve stimulation apparatus is 2 Hz or more and 2.5 Hz or less. Equipped with an electrocardiogram signal detection unit that detects the heart rate of the patient to be stimulated,
The controller is
The frequency below the frequency corresponding to the allowable upper limit heart rate in the second stimulation waveform is set according to the heart rate of the patient detected by the electrocardiogram signal detection unit. Or the nerve stimulation apparatus of 2. A nerve stimulation device for stimulating nerves from inside a blood vessel,
A stimulation electrode for applying electrical stimulation through the inner wall of the blood vessel;
An electrocardiogram signal detector for detecting an electrocardiogram signal of a patient to be stimulated;
An atrial refractory period prediction unit that predicts the timing of an atrial refractory period based on the patient's electrocardiographic signal detected by the electrocardiogram signal detection unit;
A controller for controlling the current or voltage supplied to the stimulation electrode,
The control unit
As the current or voltage control pattern,
A first stimulation pattern for continuously applying a first stimulation waveform repeated at a frequency equal to or higher than a frequency corresponding to the allowable upper limit heart rate;
A second stimulation pattern for applying a second stimulation waveform for electrical stimulation at the timing of the atrial refractory period predicted by the atrial refractory period prediction unit;
Having
Neural stimulator.

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