JP5470650B2 - Myocardial action potential measurement probe and myocardial action potential measurement method - Google Patents

Description

  The present invention relates to a probe for measuring myocardial action potential and a method for measuring myocardial action potential.

  Measurement of the action potential of the myocardium is important for heart research and drug development. The action potential of cardiomyocytes can be measured by a patch clamp method in which a fine glass electrode is adsorbed on the myocardial cell membrane. On the other hand, the average action potential of myocardial tissue in which a plurality of myocardial cells are aggregated (hereinafter referred to as myocardial action potential) is adsorbed by inserting a fine glass electrode into the myocardial tissue or by pressing the electrode into the myocardial tissue. It can be measured by the Frank method. However, it is difficult to apply these methods to the heart moving by breathing or pulsation.

  In view of such circumstances, the present inventor has developed a method for measuring the action potential of the heart during exercise by inserting a needle-like electrode into the myocardium.

Junko Saito, Shinichi Niwano, Hiroe Niwano, Takayuki Inomata, Yoshihiro Yumoto, Kazuko Ikeda, Kimiatsu Inouo, Jisho Kojima, Minoru Horie, and Tohru Ishuzumi, "Elecrical Remodeling of Ventricular Myocardium in Myocarditis -Studies of Rat Experimental Autoimmune Mycarditis" Journal Vol. 66, 97-103, 2002.

  However, even in this method, due to the movement of the heart of the experimental animal, the insertion electrode swings along the insertion path in the myocardial tissue, and the electrical contact between the insertion electrode and the myocardial tissue tends to be poor. When a contact failure occurs between the insertion electrode and the myocardial tissue, noise is induced in the measurement signal, and the SN ratio (signal to noise ratio) of the electrocardiogram (a graph representing the relationship between the myocardial action potential and time) deteriorates. This noise is extremely detrimental to the measurement of monophasic action potential (MAP), which is important for heart research.

  SUMMARY OF THE INVENTION An object of the present invention is to provide a myocardial action potential measurement probe and a myocardial action potential measurement method that suppress the generation of noise caused by respiratory motion and heart pulsation.

  In order to achieve the above object, according to a first aspect of the present invention, there is provided a flexible coated conductive wire having a conductive wire and a coating covering the conductive wire, and a penetration electrode inserted into the myocardium. A probe for measuring the myocardial action potential is provided in which the insertion electrode is fixed to the tip of the covered conducting wire and is electrically connected to the conducting wire.

  Moreover, according to the 2nd viewpoint of this invention, it has a flexible covering conducting wire which has a conducting wire and the film which coat | covers the said conducting wire, and the piercing electrode pierced by the myocardium, A first step of inserting the insertion electrode of the probe for measuring a myocardial action potential fixed to the distal end of the covered conductor and electrically connected to the conductor; and the covered conductor A second step of applying a force to the first part and pressing the tip against the heart to bend the covered conducting wire between the tip and the first part; and the tip and the first A third step of fixing the second portion of the covered conductor while the space between the portions is bent, and a step of measuring a voltage between the reference electrode and the insertion electrode attached to the living body having the heart A method for measuring myocardial action potential having four steps is provided.

  According to the present invention, it is possible to measure the myocardial action potential while suppressing the generation of noise due to respiratory motion and heart beat.

It is sectional drawing of the probe for myocardial action potential measurement of embodiment. It is a figure explaining the structure of the myocardial action potential measuring system used for the measuring method of the myocardial action potential of embodiment. It is a figure explaining the process of mounting | wearing the heart of an experimental animal with the probe for myocardial action potential measurement. It is a figure explaining MAP measured by an embodiment. It is a figure explaining the process of mounting | wearing the heart of an experimental animal with the probe for myocardial action potential measurement of a comparative example. It is a figure explaining MAP measured by the comparative example.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. However, the technical scope of the present invention is not limited to these embodiments, but extends to the matters described in the claims and equivalents thereof. In addition, the same code | symbol is attached | subjected to the corresponding part even if drawings differ, and the description is abbreviate | omitted.

(1) Configuration of Myocardial Action Potential Measurement Probe FIG. 1 is a cross-sectional view of a myocardial action potential measurement probe 2 of the present embodiment.

  As shown in FIG. 1, the myocardial action potential measurement probe 2 of the present embodiment has a flexible covered conductor 8 having a conductor 4 and an insulating film 6 that covers the conductor 4. . Here, the conducting wire 4 is, for example, a twisted wire formed by twisting a plurality of fine nickel-cobalt alloy wires or a plurality of copper wires. Moreover, the film 6 is a film formed of, for example, polyurethane or silicone. The flexibility of the coated conductor 8 (the property of bending when pressed with one end fixed and returning the shape to the original straight line when the pressing force is removed) is due to the elasticity of the polyurethane or silicone. An example of such a coated conductor 8 is a pacemaker lead. The length of the covered conductor 8 is, for example, 0.1 to 2.0 m.

  The myocardial action potential measurement probe 2 has an insertion electrode 10 which is inserted into the myocardium. As shown in FIG. 1, the penetration electrode 10 of the present embodiment is a conductive needle made of platinum or tungsten. Here, the insertion electrode 10 is electrically connected to the tip of the conducting wire 4 by solder or a crimping sleeve. In addition, the insertion electrode 10 is fixed to the tip of the covered conductor 8 by a heat shrinkable tube 12.

  Here, the length of the insertion electrode 10 is, for example, 1 to 5 mm. Moreover, the diameter of the penetration electrode 10 is 0.1-0.4 mm. Thus, the penetration electrode 10 of this Embodiment is a fine electrode. However, when the experimental animal is large, the insertion electrode may be larger.

  The myocardial action potential measurement probe 2 has a connection terminal (plug) 14 provided at the end of the covered conductor 8. The terminal of the conducting wire 4 is electrically connected to the electrode 16 of the connection terminal 14.

(2) Method for Measuring Myocardial Action Potential Next, a method for measuring myocardial action potential using the myocardial action potential measuring probe 2 of FIG. 1 will be described. FIG. 2 is a diagram for explaining the configuration of the myocardial action potential measurement system 18 used in the myocardial action potential measurement method of the present embodiment. FIG. 2 also shows an experimental animal 34 and an experimental table 32 that are measurement targets.

  As shown in FIG. 2, the myocardial action potential measurement system 18 used in the present method has the above-described myocardial action potential measurement probe 2 and a cable 22 composed of a coated conducting wire 20 provided with a reference electrode 19 at the tip. ing. The reference electrode is, for example, a stainless steel hook electrode.

  The myocardial action potential measurement system 18 includes a living body amplifier (polygraph) 26 to which the connection terminal 16 of the myocardial action potential measurement probe 2 and the connection terminal 24 provided at the end of the cable 22 are connected, and a living body amplifier. An analog-digital converter 28 connected to the computer 26 and a computer 30 connected to the analog-digital converter 28 are included.

  The myocardial action potential measurement method of the present embodiment is performed according to the following procedure using this system.

(I) Treatment of Experimental Animal First, the chest of the experimental animal (mouse, rat, etc.) 34 is opened on the experimental table 32 to expose the heart 36 (see FIG. 2). Thereafter, the reference electrode 19 at the tip of the cable 22 is fixed to the subcutaneous tissue of the chest wall of the experimental animal 34. That is, the reference electrode 19 is attached to a living body (experimental animal 34) having a heart 36. Thereafter, the cable 22 is fixed to the experimental table 32 with, for example, an adhesive tape (not shown).

(Ii) Insertion Step FIG. 3 is a diagram illustrating a step of mounting the myocardial action potential measurement probe 2 on the heart of an experimental animal. In FIG. 3, the experimental animal body (excluding the heart) is omitted.

  In this step, as shown in FIG. 3A, the insertion electrode 10 is inserted into the moving heart 36 with the portion P1 of the coated conductor 8 close to the insertion electrode 10.

(Iii) Bending step and fixing step Next, the part P2 behind the part P1 is gripped, and the hand is released from the part P1. Thereafter, a force is applied to the part P2 to press the tip 38 of the covered conductor 8 against the heart 36, and the covered conductor 8 is bent between the tip 38 and the part P2 (see FIG. 3B).

  Next, a part slightly rearward from the part P2 is fixed to the experimental table 32 with, for example, the adhesive tape 40 while the gap between the tip 38 and the part P2 is bent (see FIG. 3B). Thereafter, the rear portion is fixed with the adhesive tape 40 a, and the coated conductor 8 is securely fixed to the experimental table 32.

  As described above, the covered conductor 8 inserts the insertion electrode 10 into the moving heart 36 and applies a force to a part (part P2) of the covered conductor 8 to press the insertion electrode 10 against the heart 36. Sometimes, it is formed to bend between the tip 38 and the portion (part P2).

  By the way, the heart 36 is constantly beating. In addition, the entire heart is shaking as the experimental animal breathes. When the movement of the heart 36 cannot be followed, the insertion electrode 10 moves around the myocardial tissue along the insertion path.

  However, according to the present embodiment, the distal end 38 is always pressed against the heart 36 due to the bending of the covered conductor 8, so that the insertion electrode 10 moves following the movement of the heart. Therefore, the insertion electrode 10 does not move around in the myocardial tissue. That is, the insertion electrode 10 is fixed to the myocardial tissue.

(Iv) Action Potential Measurement Step Next, the voltage between the reference electrode 19 and the insertion electrode 10 is amplified by the biological amplifier 26. Next, this voltage is converted into a digital signal by the analog-digital converter 28. Thereafter, the digital signal is captured by the computer 30 and recorded on the hard disk (not shown). This voltage recording continues during the experiment on the experimental animal (eg, the experiment examining the response to the drug). As described above, the voltage between the reference electrode 19 and the insertion electrode 10 is measured.

  The computer 30 graphs the data corresponding to the voltage recorded in the hard disk and outputs it to a display screen or a printer (not shown) in response to an operator command during and after the experiment.

  The biological amplifier 26 has a band-pass filter that can set the cutoff frequency of the pass band to a desired value. In the normal measurement of the myocardial action potential, the cutoff frequency on the low frequency side is set to 50 Hz, for example, and the cutoff frequency on the high frequency side is set to 300 Hz. When the cutoff frequency on the low frequency side is set to 50 Hz, a sudden change in myocardial action potential accompanying cell membrane depolarization can be measured, but a gradual change in myocardial action potential accompanying cell membrane repolarization cannot be measured. .

  Such a gentle change in myocardial action potential accompanying repolarization can be measured by setting the low-frequency cutoff frequency to, for example, 0 to 5 Hz. The myocardial action potential measured by such a method is called a monophasic action potential (MAP), and its importance has attracted attention in recent years.

  FIG. 4 is a diagram for explaining the MAP measured according to the present embodiment. The cut-off frequency on the low frequency side of the bandpass filter during measurement is 5 Hz, and the cut-off frequency on the high frequency side is 300 Hz. The horizontal axis is time, and the vertical axis is myocardial action potential.

  As shown in FIG. 4, the MAP measured according to the present embodiment is a clear electrocardiogram with a high S / N ratio.

  If the electrical contact between the myocardial tissue and the insertion electrode 10 is not good, noise from a commercial AC power supply or the like (for example, frequency 50 Hz) is induced in the input signal of the biological amplifier 26. By the way, in the MAP measurement, as described above, the cutoff frequency on the low frequency side is set to several Hz or less. For this reason, when low frequency noise from a commercial AC power supply or the like is superimposed on the input signal of the biological amplifier 26, the biological amplifier 26 cannot remove this noise and amplifies it as it is. As a result, a noisy MAP is measured.

  However, according to the present embodiment, the tip 38 is always pressed against the heart 36 by the bent covered conductor 8. For this reason, since it moves following the movement of the heart 36, the insertion electrode 10 does not move around in the myocardial tissue. That is, the insertion electrode 10 is fixed to the myocardial tissue. Therefore, the electrical contact between the myocardial tissue and the insertion electrode 10 is always good and almost no noise is generated. Therefore, the S / N ratio of MAP becomes high.

(3) Comparative Example The configuration of the myocardial action potential measurement probe of this comparative example is substantially the same as the configuration of the myocardial action potential measurement probe 2 of the above embodiment. However, the coated conducting wire of this comparative example is a coated conducting wire in which a copper twisted wire is coated with polyvinyl chloride. This covered conductor is an electric cable widely used for internal wiring of an electric device. Since this covered conductor is inflexible, it is bent when an external force is applied, and does not return to its original shape.

  FIG. 5 is a diagram illustrating a process of mounting the myocardial action potential measurement probe 2a of this comparative example on the heart 36 of the experimental animal. In FIG. 5, the experimental animal body (excluding the heart) is omitted.

  First, as in the above embodiment, the insertion electrode 10 of the myocardial action potential measurement probe 2a is inserted into the heart 36 with the portion P3 of the coated conductor 8 close to the insertion electrode 10 (FIG. 5). (See (a)). The myocardial action potential measurement probe 2a is folded in a folded state when no measurement is performed. Therefore, the covered conductor 8a is bent in some places as shown in FIG.

  Next, the part P4 behind the part P3 is grasped, and the hand is released from the part P3. Thereafter, a force is applied to the part P4 to lightly press the tip 38 of the covered conductor 8a against the heart 36 (see FIG. 5B). At this time, the covered conductor 8a is not bent.

  Next, as shown in FIG. 5B, a part slightly behind the part P <b> 4 is fixed to the experimental bench 32 with, for example, an adhesive tape 40. Thereafter, the rear portion is fixed with the adhesive tape 40 a, and the coated conductor 8 a is securely fixed to the experimental table 32.

  FIG. 6 is a diagram for explaining the MAP measured by this comparative example. The measurement conditions are the same as in the above embodiment. The horizontal axis is time, and the vertical axis is myocardial action potential.

  As shown in FIG. 6, the MAP measured by this comparative example is an electrocardiogram with a low S / N ratio including a large noise.

  In this comparative example, as described above, the coated conductor 8a does not bend. For this reason, the covered lead 8 cannot follow the movement of the heart 36, and the insertion electrode 10 moves around in the myocardium. As a result, the electrical contact between the myocardial tissue and the insertion electrode 10 becomes poor, noise is induced in the input signal of the bioamplifier 26, and MAP with a low S / N ratio is measured.

  In the above embodiment, the present invention is applied to the measurement of MAP. However, the present invention can be applied to other myocardial potential measurements. For example, a normal electrocardiogram may be measured by setting the cut-off frequency on the low frequency side to about 50 Hz.

  In the above example, the measurement object is an experimental animal. However, the present invention may be applied to the human body to collect data necessary for diagnosis of heart disease, for example.

2 ... Probe for measuring myocardial action potential 4 ... Conductor 6 ... Coated 8 ... Coated conductor 10 ... Insertion electrode 20 ... Coated conductor 38 ... Tip

Claims (1)

A flexible coated conductive wire having a conductive wire and a coating covering the conductive wire; and a piercing electrode inserted into a myocardium, wherein the piercing electrode is fixed to a tip of the coated conductive wire, and the conductive wire A first step of inserting the insertion electrode of the probe for measuring myocardial action potential electrically connected to the heart into a moving heart;
Said the first part of the coated conductive wire by applying a force by pressing the tip into the heart (except human heart), between the said distal end first portion, the deflecting said coated conductive wire Two steps;
A third step of fixing the second part of the covered conductor while the gap between the tip and the first part is bent;
A fourth step of measuring a voltage between a reference electrode attached to the living body having the heart and the insertion electrode;
A method for measuring myocardial action potential.

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