JP2002200052A - Vascular endothelium function tester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a vascular endothelium function tester by which ever an unskilled skilled operator can precisely measure a vascular endothelium function without applying a large load to a subject. SOLUTION: Constant current electrodes 41, 42 are put on in between the shoulder part and the wrist part of the upper arm of a subject and micro-high- frequency constant current is applied from a constant current supplying part 40. Impedance between voltage electrodes 51, 52 put on at a prescribed distance 'L' on the upper arm is measured by a cuff 22 for hemodynamometry/ avascularization before and after avascularization of the upper arm part. The variation rate of impedance measured by the impedance converting part 50 is compared therewith and calculated by a before and after avascularization comparing part 11. The impedance variation is caught as a blood flow rate variation and the variation rate is referred to the vascular endothelium function to make a measurement index of the vascular endothelium function taking a vascular area and other blood flow speed variation, etc., in consideration.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a vascular endothelial function measuring apparatus capable of measuring a vascular endothelial function by measuring a vasodilatory response before and after avascularization.

[0002]

2. Description of the Related Art Vascular endothelial cells are stimulated by acetylcholine or mechanical stress (or shear stress) to produce nitrogen oxides, that is, EDRF (Nitric Oxide).
Or nitrogen oxide analogs) to produce and release vascular tonus, which has been found to regulate the vascular tonus, and that EDRF (NO) -mediated endothelium-dependent vasorelaxation is reduced in atherosclerotic blood vessels. Have been reported.

[0003] For these reasons, in recent years, an abnormal function of vascular endothelial cells has been pointed out as an early lesion of arteriosclerosis. And it is increasingly recognized that this decrease in vascular endothelial function is an initial change in arteriosclerosis.

[0004] Therefore, by measuring the endothelium-dependent vasorelaxation reaction mediated by EDRF (NO), it is possible to detect a functional abnormality of vascular endothelial cells, and to easily find an early lesion of arteriosclerosis. It can be carried out.

As a conventional method for measuring the endothelium-dependent vasorelaxant response via EDRF (NO), acetylcholine or the like is administered into the coronary artery by an invasive method using a catheter or the like, and the dilatation of the blood vessel is examined. The way was being taken.

[0006] However, such an invasive method requires a great deal of labor for measurement, and imposes a great burden on the patient. For this reason, a non-invasive method using an ultrasonic device has been invented, and a method for examining a blood flow-dependent vasodilation reaction in the brachial artery has been performed as an endothelium-dependent vasodilation reaction.

In a conventional non-invasive method using an ultrasonic device, for example, a measuring terminal is positioned and arranged at a predetermined portion of an arm,
The state of the blood vessel in the resting state is detected, and the diameter of the blood vessel is detected. Thereafter, the blood vessel at the predetermined site is avascularized for a predetermined time, for example, 5 minutes. After the release of the avascularization, the measurement terminal is positioned and arranged again at the measurement site of the vascular system at the time of rest, and the blood vessel diameter at the positioning and placement position after a predetermined time after the release of the avascularization, for example, 15 minutes after the release of the avascularization, is detected. . And the dilation rate of the blood vessel was measured.

[0008]

However, the diameter of the blood vessel is not so large, and the expansion ratio of the blood vessel must be determined. The measurement terminals must be arranged at exactly the same position before and after the avascularization. Measurement accuracy could not be ensured. For this reason, a highly accurate detection result could not be obtained without a great deal of skill.

In other words, the non-invasive method using an ultrasonic device simply measures the diameter of a blood vessel at a specific site, does not reflect the peripheral endothelial function, and uses an expensive ultrasonic diagnostic device. It takes heat to obtain a long-axis B-mode image of a blood vessel, and it is necessary to use an image analysis device or the like to obtain objectivity or reproducibility in blood vessel measurement. There was a problem with the spread.

[0010] Further, during the examination period, there is also an operation of using a nerve which restrains the subject while the ultrasonic sensor is fixed.

[0011]

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and provides a stable measurement environment without imposing a great load on a subject and without much skill. It is an object of the present invention to provide a vascular endothelial function measurement device capable of measuring vascular endothelial function with high accuracy. For example, the following configuration is provided as one means for achieving such an object.

That is, a constant current supply means for supplying a predetermined constant current between first biological electrodes mounted on predetermined portions of the limbs of the subject separated from each other by a predetermined distance, and a predetermined distance between the biological electrodes Voltage detecting means for measuring a voltage value between the second living body electrodes attached to the part, a cuff control means for pressurizing and controlling a cuff wound around a predetermined part of the upper arm, and the cuff control means. A control means for controlling the pressure inside the cuff to pressurize the internal pressure of the cuff for a fixed time to exhale the upper arm for a fixed time; and controlling the blood drive based on the voltage detected by the voltage detecting means and the supply current of the constant current supply means. Impedance measuring means for measuring the bioimpedance between the second bioelectrodes before and after a predetermined period of time after the excursion by the means, and after a certain period of time after the excision of blood for a certain period of time; Seeking changes in the amount, characterized in that it comprises a derivation means for deriving a vascular endothelial function than the amount of change before and after the avascularization.

[0013] For example, the apparatus further comprises pulse measuring means for measuring a pulse rate, wherein the deriving means is for one minute from the blood volume obtained from the bioelectrical impedance measured by the impedance measuring means and the pulse rate measured by the pulse measuring means. Is obtained, and the vascular endothelial function is derived from the blood volume before and after the avascularization and the change amount of the one-minute pulse volume.

Also, for example, the deriving means obtains a change in blood flow between the second biological electrodes before and after avascularization based on the bioelectrical impedance measured by the impedance measuring means, and obtains a blood vessel area and a blood flow. It is characterized by estimating a rate of change of a speed element.

A constant current supply means for supplying a predetermined constant current between the first living electrodes mounted on a predetermined portion of the limb of the subject separated from the living body by a predetermined distance; Voltage detecting means for measuring a voltage value between the second living body electrodes attached to the subject, cuff control means for controlling pressurization of a cuff wound around a predetermined part of the subject, and the cuff control means Controlling the blood pressure in the cuff for a certain period of time to exfoliate the upper arm for a certain period of time; and detecting the second voltage based on the voltage detected by the voltage detecting unit and the supply current of the constant current supplying unit. Impedance measuring means for measuring bioimpedance between the biological electrodes, blood flow detecting means for detecting blood volume and blood flow in a blood vessel between the cuff and the second electrode, and detection by the blood flow detecting means Before and after perfusion Characterized in that it comprises a derivation means for deriving the estimated vascular endothelial function the rate of change of the vascular area and the blood flow velocity component than of quantity.

For example, the blood flow detecting means further transmits and receives an ultrasonic signal, detects a blood flow velocity by the Doppler effect accompanying blood flow in the limbs, and detects a blood volume and a blood flow in a blood vessel. The deriving means derives a blood vessel area or a blood vessel diameter change by dividing a blood flow detected by the blood flow detecting means by a blood flow velocity.

For example, the blood pressure measuring means for measuring the blood pressure of the subject is provided, and the deriving means derives the vascular endothelial function with reference to the change in blood pressure before and after the avascularization measured by the blood pressure measuring means. It is characterized by the following. Alternatively, the apparatus further comprises a pulse measuring means for measuring a pulse rate, wherein the deriving means includes a one minute pulse output from the blood flow rate obtained from the bioelectrical impedance measured by the impedance measuring means and the pulse rate measured by the pulse measuring means. , The peripheral vascular resistance is determined from the determined one-minute pulse output, and the vascular endothelial function is derived from the blood flow before and after the avascularization and the peripheral vascular resistance.

Further, a nitrogen oxide production amount detecting means for detecting a nitrogen oxide production amount in a blood vessel of the subject, and a blood vessel based on the nitrogen oxide production amount detected by the nitrogen oxide production amount detecting means. Deriving means for deriving an endothelial function, wherein the nitrogen oxide production amount detection means detects a nitrogen oxide production amount by measuring a change in a blood vessel diameter before and after applying a mechanical stress to the blood vessel. .

For example, the nitrogen oxide production amount detecting means utilizes a phenomenon in which the blood vessel is relaxed due to the production of nitrogen oxide to avascularize a blood vessel within a measurement range for a predetermined period of time, and a blood vessel within a predetermined range before and after the avascularization. Is characterized in that the output of nitrogen oxides is estimated by measuring the impedance of the nitrogen oxides.

Further, for example, the nitrogen oxide production amount detecting means further includes a blood flow detecting means for detecting a blood flow in the blood vessel, and a peripheral resistance value and a blood vessel diameter are obtained from the measured bioimpedance value and blood flow value. , The maximum blood flow velocity and the average blood flow velocity, and the amount of nitrogen oxide produced in the blood vessel is detected from the change rate of the blood vessel diameter.

Further, for example, the deriving means derives a vascular endothelial function based on the rate of increase in the amount of nitrogen oxide every predetermined time after applying mechanical stress to the blood vessel detected by the nitrogen oxide production amount detecting means. It is characterized by doing.

[0022] In addition, an avascularization means for advancing a blood vessel at a measurement site of the subject, an impedance measurement means for measuring a bioimpedance of the measurement site of the subject before and after the avascularization by the avascularization means, and Vasodilatory change detecting means for detecting a change in arterial vascular diameter of a predetermined portion of the subject before and after the avascularization by the avascularizing means from the bioelectrical impedance measured by the measuring means, and arterial vasodilation detected by the vasodilatory change detecting means A deriving means for deriving a vascular endothelial function based on the change.

Further, for example, the vasodilatory change detecting means detects a peripheral arterial vasodilatory change from the measured impedance fluctuation of the impedance measuring means, and detects a vascular resistance change in arterioles and capillaries from the basal impedance fluctuation. It can be output to the deriving means.

Further, for example, the apparatus further comprises pulse measuring means for measuring a pulse rate, wherein the vasodilatory change detecting means comprises a blood volume obtained from the bioelectrical impedance measured by the impedance measuring means and a pulse rate measured by the pulse measuring means. From
It is characterized in that a stroke volume per minute is obtained, a peripheral vascular resistance is obtained from the calculated stroke volume per minute, and a vascular endothelial function is derived from the blood volume before and after the avascularization and the peripheral vascular resistance.

Further, for example, a blood flow detecting means for detecting a blood flow in a blood vessel is further provided, and a change in peripheral arterial vasodilation before and after the avascularization by the avascularization means can be quantified. Alternatively, the blood flow detecting means transmits and receives an ultrasonic signal, detects a blood flow velocity by a Doppler effect accompanying blood flow at a measurement site, detects blood volume and blood flow in a blood vessel, and detects the vasodilation change. The means derives a blood vessel area or a blood vessel diameter change by dividing a blood flow detected by the blood flow detecting means by a blood flow velocity.

[0026]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A vascular endothelial function measuring apparatus according to an embodiment of the present invention will be described below in detail with reference to the drawings.

In recent years, when shear stress acts on blood vessels, the production of nitrogen oxides, specifically nitric oxide (NO) and prostacyclin, from vascular endothelial cells increases, and the expression of adhesion molecules also changes. It has been found that many endothelial functions are modified. Therefore, by detecting the state of the blood vessel before and after the avascularization, it becomes possible to identify the vascular endothelial function.

The response of endothelial cells to shear stress includes "increase in NO production" as a response occurring within minutes, and "increase in production of prostacyclin," activation of protein kinase ", Changes in plaques "" Expression of immediate early gene "
If these can be measured, the vascular endothelial function can be identified.

Therefore, in this embodiment, "N"
Focusing on "increase in O production," measuring blood flow, blood flow velocity, and peripheral vascular resistance by focusing on the fact that the blood vessel diameter expands due to "increase in NO production," Is characterized in that an index for discriminating vascular endothelial function can be provided by comparing the values of.

Specifically, it is characterized in that the vascular endothelial function is measured by measuring the electrical impedance of, for example, the hand (upper arm) or foot (lower limb) of the subject. By simultaneously obtaining blood pressure values, blood flow changes, peripheral arterial vasodilatory changes, peripheral vascular resistance, etc. can be provided independently for the purpose of knowing the degree of progression of arteriosclerosis, Provide an indicator.

For example, blood flow changes and peripheral arterial vasodilation changes are determined from impedance variations, and vascular resistance changes in arterioles and capillaries are determined from basal impedance changes.

Since these indices are relative comparisons, they are not affected by the biological intrinsic constant, and it is possible to compare results with different dates and times and between people.

In addition to the electrical impedance measurement, the blood flow velocity in the blood vessel can be measured by a Doppler blood flow sensor, and the measurement is performed simultaneously with the bioelectrical impedance measurement on the target blood vessel to quantify the vascular dilatation change of the peripheral artery. Provide a means to do so.

Furthermore, by simultaneously measuring arterial blood pressure of the upper arm and the like, it is possible to provide a means for measuring and displaying local peripheral resistance between the amount of blood ejection in peripheral arteries obtained by bioelectrical impedance measurement. I do. Furthermore, a new measuring means for evaluating the degree of autonomic nerve involvement in vasodilation can be provided.

By providing accurate information reflecting the above vascular endothelial function, it can be applied to diagnosis, treatment and prevention of heart disease and hypertension, and is safe and easy for a wide range of subjects from children to adults. Inexpensive inspection means can be provided.

That is, by applying the bioelectrical impedance method to an arm or a lower limb, which is a simple model, it can be realized with a simple configuration without requiring skill and an electrode can be applied to a subject. Even when a simple measurement of Doppler blood flow described below is performed, various indices for evaluating the vascular endothelial function can be obtained with the detection unit mounted on a certain site. Furthermore, synchronization at an arbitrary time can be tracked by synchronizing with the inherence waveform or the blood flow waveform.

As a result, it is possible to provide a means for simply and quantitatively measuring blood vessel endothelial function, and it can be widely applied to prediction, diagnosis, prevention and treatment of coronary artery disease, hypertension, and occlusive artery disease caused by arteriosclerosis. Become. This will be specifically described below.

[Embodiment] FIG. 1 is a view for explaining a basic configuration of a vascular endothelial function measuring apparatus according to an embodiment of the present invention, and FIG. 2 is a view showing a detection unit for a subject. It is a figure for explaining a wearing normal condition.

In the figure, reference numeral 10 denotes an arithmetic and control unit which controls the overall control of the apparatus according to the present embodiment, and incorporates a before-and-after blood transfusion comparing unit 11 which will be described in detail later. The arithmetic control unit 10 calculates, from data obtained from the impedance measured via the impedance conversion unit 50, the Zo, ΔZ separation unit 62, and the like,
The maximum value, the average value of the flow value, the blood flow for one minute are calculated, and the peripheral resistance is calculated from the blood pressure value obtained from the blood pressure measurement and the avascularization control unit 20 and the blood flow velocity value detected using the Doppler blood flow measurement unit 30. Value, blood vessel area (diameter), maximum blood flow velocity value, and average blood flow velocity value. Further, the display unit 70, the recording unit 75, the storage unit 80, the sound generation unit 85 and the like can be controlled.

Further, the built-in pre- and post-vascularization comparison unit 11 compares the various measured values and the measurement results obtained by the arithmetic and control unit 10 before and after the avascularization, and calculates a diagnostic index. Comparison of blood flow before and after blood flow, comparison of blood flow velocity, comparison of peripheral vascular resistance, comparison of blood vessel area (diameter), comparison of blood pressure value, and the like can be performed. Then, the vascular endothelial function is derived from the above index, and the result can be displayed on the display unit 70 or recorded and output on the recording unit 75, and can be stored in the storage unit 80.

It is also possible to measure the pulse rate before and after cardiovascularization using the blood pressure measurement / cardiographic cuff 22 or the like. One minute is determined from the blood flow rate obtained from the measured bioelectrical impedance and the measured pulse rate. Vascular endothelial function can be derived from the blood flow volume before and after cardiotomy and the change amount of the cardiac output volume for one minute. That is, the ratio of the blood volume before and after the avascularization between the voltage electrodes 51 and 52 is obtained based on the measured bioimpedance, and the change rates of the blood vessel area element and the blood flow velocity element are estimated.

Reference numeral 20 denotes a blood pressure measurement and transvascularization control unit which presses the blood pressure measurement / transfusion cuff 22 and controls the measurement to measure the blood pressure of the subject, for example, before the transfusion, and to transect the forearm. Also, it is a blood pressure measurement and avascularization control unit that performs pressurization control of the wrist cuff 24 to perform wrist avascularization.

The blood pressure measurement and transvascularization control unit 20 includes the components of a normal blood pressure measurement device, for example, a pressure sensor for detecting the internal pressure of the cuff, and rubber bladders 22a, 24a of the cuffs 22, 24.
Pressurizing pump, pressurizing the cuff, reducing the internal pressure of the cuff at a constant speed, for example, a constant-speed exhaust valve for performing blood pressure measurement, etc., a rapid exhaust valve for rapidly reducing the internal pressure of the cuff, such as in the case of blood removal,
It includes a blood pressure determining unit that determines a systolic blood pressure value and a diastolic blood pressure value. Since these configurations are known, detailed description thereof will be omitted.

Numeral 21 denotes a switching valve for switching between sending the pressure control air from the blood pressure measurement and transfusion control unit 20 to the blood pressure measurement / transfusion cuff 22 or the wrist cuff 24. 2
Reference numeral 2 denotes a blood pressure measurement / wrapping around the forearm (or upper arm) of the subject, and a blood pressure measurement /
A cuff for blood augmentation 24 is a cuff for a wrist for performing a blood cuff for a wrist as needed.

Reference numeral 30 denotes a blood flow measuring unit for detecting a blood flow velocity in a blood vessel using the Doppler effect using ultrasonic waves;
Is a detection unit, which transmits an ultrasonic signal of a predetermined frequency from near the tip of the detection unit (Doppler sensor) 35,
A received signal reflected from, for example, the upper arm of the subject is detected, and the blood flow velocity of the blood in the blood vessel at the position where the subject is mounted with the detector 35 is measured. The principle and configuration of detecting a blood flow velocity in a blood vessel using the Doppler effect are known, and thus detailed description is omitted.

In the present embodiment, the blood flow measuring section 30 has a built-in oscillating section for oscillating an ultrasonic signal of, for example, 5 MHz to 10 MHz, and transmits / receives an ultrasonic signal from the oscillating section from the detecting section 35. In addition, the blood flow velocity by the known Doppler effect can be detected from the degree of delay of the received ultrasonic signal.

Reference numeral 40 denotes a low current supply unit which can supply a constant current of a predetermined frequency between the constant current electrodes 41 and 42, and includes, for example, an oscillation circuit for oscillating a signal of 60 KHz and a constant current source. Reference numeral 50 denotes an impedance conversion unit that detects an impedance value (bioimpedance) between the voltage electrodes 51 and 52 mounted between the constant current electrodes 41 and 42 supplied by the constant current supply unit 40. It is desirable to use an Ag-Agcl electrode or the like for the voltage electrodes 51 and 52 in order to obtain a stable measurement result.

When a minute high-frequency current flows between the voltage electrodes 51 and 52, a voltage proportional to the impedance of the tissue existing between the electrodes is detected at both electrodes. In areas where there is no other organ such as the upper arm or the lower limb, the voltage electrodes 51, 5
The impedance detected between the two is mainly affected by the blood pumped from the heart. Therefore, the voltage electrodes 51, 5
By measuring the impedance between the two, it is possible to determine the amount of stroke flowing through the site, and to derive the blood flow and the like.

Reference numeral 61 denotes a flow rate measuring section for measuring the blood flow rate in the blood vessel from the impedance value from the impedance converting section 50, and the differential value (d
Z / dt) can be detected. 62 is a Zo, ΔZ converter that separates and outputs the basal impedance term (Zo) variation ratio and ΔZ term variation ratio before and after avascularization from the impedance value from the impedance converter 50, and 63 is the impedance value from the impedance converter 50 This is a synchronization detection unit that detects synchronization with a heartbeat or the like from fluctuations in the heart rate.

Reference numeral 70 denotes a display unit capable of displaying various operation guidance, measurement results, and diagnostic indices; 75, the measurement results;
The recording units 1 and 80 capable of recording and outputting diagnostic indices are measurement results,
This is a storage unit for storing a diagnostic index, and a large-capacity external storage device or the like is applicable. Reference numeral 85 denotes a voice generation unit that can output guidance by voice and various notification sounds.

In this embodiment having the above configuration, a method of mounting various sensors on the subject will be described with reference to FIG. The part to which the constant current electrodes 41 and 42 are attached, that is, the measurement part of the subject, is a simple model part in which blood can be ablated in the body of the subject and a blood vessel is most simply arranged, for example, a lower limb or an upper arm It is desirable to mount them at a predetermined distance from each other.

In this embodiment, a case where the upper arm is used as a measurement site will be described as an example. The following description will be made with reference to the example of FIG. 2 in which the voltage electrodes 51 and 52 are attached to the upper arm and the blood pressure measurement / blood-compensation cuff 22 is attached to the forearm. However, the present invention is not limited to this example. Similar measurement results can be obtained by attaching the cuff 22 for measuring and advancing blood pressure to the upper arm and attaching the voltage electrodes 51 and 52 to the forearm. Thus, the mounting site can be arbitrarily selected.

The measurement site is not limited to the arm, but the lower limb may be used as the measurement site, and it goes without saying that other sites may be used.

In this embodiment shown in FIG. 2, one constant current electrode 41 is attached to the upper arm portion, and the other constant current electrode 42 is attached to the wrist or back of the hand. When measuring the impedance, the two electrodes 4 are used.
A constant current of a predetermined frequency is applied between the terminals 1 and 42.

Then, other sensors are mounted between the two electrodes. The voltage electrodes 51 and 52 are mounted on the uppermost side (upstream side of the blood flow) of the upper arm via a voltage electrode fixing jig 55 for positioning and fixing the distance between the voltage electrodes 51 and 52 to a predetermined distance, for example, an interval of “L”. . The electrode may be mounted in any manner as long as the voltage electrode fixing jig 55 and the electrodes 51 and 52 do not come off.

The voltage electrode 5 via the voltage electrode fixing jig 55
The reason for positioning and fixing the separation distance between the first and the second 52 at a predetermined distance, for example, “L” is to facilitate relative comparison of measurement results before and after avascularization, and to accurately detect even a slight change. It is. As a result, even if the subject changes,
Alternatively, even if the measurement date is changed, the separation distance can be kept constant, and a quantitative measurement result can be obtained.

Then, on the downstream side (lower part) of the voltage electrode 52b.
The detection unit 35 is positioned and fixed at the outer skin position of the blood vessel.
A cuff 2 for blood pressure measurement / avascularization in the downstream portion near the detection unit 35
Position and mount 2. Then, if necessary, a wrist cuff 24 is attached further downstream.

Although the wrist cuff 24 is worn in the example shown in FIG. 2, the wrist cuff 24 is used when considering the influence of blood circulation in the hand, and the wrist cuff 24 and the switching The valve 21 may be omitted and used.

The method of measuring the vascular endothelial function according to the present embodiment equipped with the sensors as described above will be described below with reference to the flowchart of FIG.

In this embodiment, first, in step S1 of FIG. 3, the sensors are mounted on a predetermined portion of the subject as shown in FIG. When the mounting is completed, the process proceeds to step S2, in which the arithmetic and control unit 10 switches the switching valve 21 to the blood pressure measurement / blood-compensation cuff 22 side, activates the blood pressure measurement and blood-compression control unit 20, and activates the subject. The blood pressure is measured, particularly the systolic blood pressure value.

When a blood pressure value is measured from a finger or when a blood pressure measurement is manually performed by a doctor or the like, the blood pressure measurement in step S2 is performed first, and then the step S2 is performed.
One sensor may be mounted.

Then, the process proceeds to a step S3, wherein a measurement process of the blood vessel state before the avascularization is performed. Here, measurement data (control data) from various sensors before the cardiovascularization is acquired. Here, the bioelectrical impedance between the voltage electrodes 51 and 52 is measured by the impedance conversion unit 50, and the blood flow velocity is measured by using the Doppler blood flow measurement unit 30 and the detection unit 35.

As a result, the base impedance Zo before the avascularization by the Zo and ΔZ separation unit 62, the impedance change ΔZ, and the blood flow volume before the avascularization (FLO
W: dZ / dt (differential value of impedance change)),
The maximum blood flow, the average blood flow, the stroke volume SV with reference to the synchronization information detected by the synchronization detection unit 63, the minute volume, PR
(Pulse rate) and the like are measured. Also, the blood pressure value B measured earlier
While acquiring P, a blood flow waveform and a blood flow waveform based on continuous impedance measurement results are obtained, and the obtained results are displayed on the display screen of the display unit 70.

Then, the obtained result is stored in the storage unit 80. The obtained result is displayed on the display screen of the display unit 70.

For example, if the impedance change measured by the impedance converter 50 is ΔZ, the blood volume change ΔV between the voltage electrodes 51 and 52 (distance L) is ΔV = ρ
(L / Zo) ² ΔZ. ΔV∝amount (cubic cm = ml), time derivative (dV / dt) ∝flow rate = area (square cm) × flow rate (cm / S).

In view of the above, it is possible to measure the following degree of vasodilatation, blood flow, etc., using only the detected impedance from the impedance conversion unit 50, and to compare it with the measurement results after avascularization described later. Thus, it is possible to provide an index of vascular endothelial function such as a change in blood flow and a blood vessel area (diameter), that is, a capability of generating nitrocellular nitric oxide.

However, even if only the flow rate is limited, if a more accurate value can be obtained, the clinical significance will be improved.
Therefore, in the present embodiment, an accurate blood flow velocity (cm / S) is provided as a configuration further including the Doppler blood flow measurement unit 30 which has no area element but can detect the blood flow velocity at the measurement site. I am getting it. The Doppler blood flow measurement unit 30 indicates the flow rate measured by the flow measurement unit 61 from the detection result of the impedance conversion unit 50 (d
V / dt).

This makes it possible to make a comprehensive judgment between the two, and even if one of the measured values does not correctly reflect the symptom, a more accurate measurement result can be obtained. For example, an ultrasonic signal is transmitted and received, the blood flow velocity is detected by the Doppler effect accompanying the blood flow in the limbs, the blood volume and the blood flow in the blood vessel are detected, and the detected blood flow is divided by the blood flow velocity. The area or blood vessel diameter change can be derived.

Next, in step S4, the arithmetic and control unit 10 confirms that the switching valve 21 has been switched to the blood pressure measurement / blood-compensation cuff 22 side, and activates the blood pressure measurement and blood-compression control unit 20. Then, the cuff 22 for blood pressure measurement / arterialization is pressurized, and the subject's upper arm is used for the predetermined period of time. In the present embodiment, the cuff internal pressure is maintained at a pressure higher by about 30 to 50 mmHg than the systolic blood pressure value measured in step S2 for about 5 minutes.

Subsequently, in step S5, after a lapse of a predetermined time (after about 5 minutes in the present embodiment), the blood pressure measurement and control unit 20 is controlled to activate a built-in quick opening valve (not shown) to control the blood pressure. The internal pressure of the cuff 22 for measurement / blood transfusion is rapidly reduced to release the blood transfusion state. Then, the process proceeds to step S6.

In step S 6, the blood vessel state is acquired at predetermined time intervals after the end of the anastomosis, and is stored in, for example, the storage unit 80. The acquisition of the blood vessel state in step S6 is performed in step S3.
Is the same as For example, the measurement is performed every minute after the end of the avascularization until 10 minutes later. Thus, for example, “NO” as a response to shear stress within several minutes of endothelial cells
The increase in the amount of production (vasodilation) of the "" is measured in chronological order.

After the measurement is completed or during the measurement, the change ratio (impedance change ratio) of each measurement of the impedance measurement waveform (marked impedance change amount) shown in step S8 is compared by the pre- and post-vascularization comparison unit 11. The state of the vascular endothelial function, such as whether the vascular endothelial function is larger or smaller than the predetermined threshold, is measured one by one. For example, it is displayed on the display unit 70 as an index of the state identification, and recorded and output from the recording unit 75. Further, it is stored in the storage unit 80 as needed.

For example, FIG. 4 shows a display example on the display unit 70 when the blood vessel state is being measured in real time, and FIG. 5 shows an output example of the analysis result in step S8.

Finally, in step S9, evaluation of the endothelial independence of the blood vessel is required based on the above measurement and analysis results.

The measurement of the present embodiment is performed by using the voltage electrode 5
For example, the degree of change in the diameter of a blood vessel at one location is different from the degree of change in the diameter of a single blood vessel as in the related art. Measurement is possible, and a change in blood flow can be easily measured.

The evaluation of the endothelium independence of the blood vessel according to the present embodiment is not an evaluation of these absolute values, but an entirely new, unconventional method that detects a change before and after cardiotomy and presents it as a ratio of the change amount. Diagnosis is possible according to the index. This makes it possible to clearly determine the criterion for determining whether the condition is normal or abnormal based on the result of comparison between the state of the healthy person and the diseased person. This result can also contribute to the prediction of coronary artery disease, and thus can provide a useful means for general arteriosclerosis diagnosis.

[0077]

According to the present invention as described above,
It is possible to provide a vascular endothelial function measurement device capable of measuring a vascular endothelial function with high accuracy without imposing a large load on the subject and without much skill.

Further, the vascular condition of the blood vessel in the measuring section of the living body before and after the avascularization can be measured by a simple operation without skill, and the vascular endothelial function is identified based on the change in the vascular condition before and after the avascularization. Therefore, it is possible to provide a common evaluation index of vascular endothelial function to a large number of subjects, which is less affected by individual differences among the subjects.

[Brief description of the drawings]

FIG. 1 is a diagram for explaining a configuration of a vascular endothelial function measuring device according to an embodiment of the present invention.

FIG. 2 is a diagram for explaining a mounted state of sensors and the like according to the embodiment.

FIG. 3 is a flowchart for explaining a procedure for measuring a vascular endothelial function according to the embodiment;

FIG. 4 is a diagram showing an example of a display screen during blood vessel state measurement according to the embodiment.

FIG. 5 is a diagram showing a display example of a blood vessel state analysis result according to the embodiment;

[Explanation of symbols]

 41, 42 Constant current electrode 51, 52 Voltage electrode 21 Switching valve 22 Cuff for blood pressure measurement / blood augmentation 24 Cuff for wrist

 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Takashi Takahashi 3-39-4 Hongo, Bunkyo-ku, Tokyo Fukuda Electronics Co., Ltd. (72) Inventor Takeshi Ishikawa 3-39-4 Hongo, Bunkyo-ku, Tokyo Fukuda Electronics Co., Ltd. (72) Inventor Mitsuya Maruyama 3-39-4 Hongo, Bunkyo-ku, Tokyo Fukuda Electronics Co., Ltd.F-term (reference)

Claims (16)

[Claims] 1. A constant current supply means for supplying a predetermined constant current between first biological electrodes attached to a predetermined portion of a limb of a subject separated by a predetermined distance, and a predetermined distance between the biological electrodes Voltage detecting means for measuring a voltage value between the second living body electrodes attached to the site where the cuff is wound, cuff control means for pressurizing and controlling a cuff wound around a predetermined portion of the upper arm portion, and cuff control means A control means for controlling the pressure inside the cuff to pressurize the internal pressure of the cuff for a predetermined time to exhale the upper arm for a predetermined time; and controlling the blood flow based on the voltage detected by the voltage detection means and the supply current of the constant current supply means. Impedance measuring means for measuring the bioimpedance between the second bioelectrodes before the blood transfusion by the means and every elapse of a predetermined time after releasing the blood transfusion for a certain time; and blood flow from the bioelectric impedance of the impedance measuring means. Seeking changes, vascular endothelial function measurement apparatus, characterized in that it comprises a derivation means for deriving a vascular endothelial function than the amount of change before and after the avascularization. 2. A pulse measuring means for measuring a pulse rate, wherein the deriving means comprises a one-minute pulse based on the blood volume obtained from the bioelectrical impedance measured by the impedance measuring means and the pulse rate measured by the pulse measuring means. 2. The vascular endothelial function measuring apparatus according to claim 1, wherein the vascular endothelial function is derived from a blood volume before and after the avascularization and a change amount of the blood volume for one minute before and after the avascularization. 3. The deriving means obtains a change in blood flow between the second bioelectrode before and after avascularization based on the bioelectrical impedance measured by the impedance measuring means, and calculates a blood vessel area and a blood flow velocity. 2. The vascular endothelial function measuring device according to claim 1, wherein a change rate of the element is estimated. 4. A constant current supply means for supplying a predetermined constant current between first bioelectrodes mounted on predetermined portions of the limbs of the subject separated by a predetermined distance, and a predetermined distance between the bioelectrodes Voltage detecting means for measuring a voltage value between the second living body electrodes attached to the subject, cuff control means for controlling pressurization of a cuff wound around a predetermined part of the subject, and cuff control means Controlling the blood pressure in the cuff for a certain period of time to exhale the upper arm for a certain period of time; and detecting the second voltage based on the voltage detected by the voltage detecting unit and the supply current of the constant current supplying unit. Impedance measuring means for measuring bioimpedance between the biological electrodes, blood flow detecting means for detecting blood volume and blood flow in a blood vessel between the cuff and the second electrode, and detection by the blood flow detecting means Changes before and after avascularization from blood flow A vascular endothelial function measuring device, comprising: a deriving unit that derives a vascular endothelial function by estimating a change rate of a blood vessel area and a blood flow velocity element from a conversion amount. 5. The blood flow detecting means further transmits and receives an ultrasonic signal, detects a blood flow velocity by a Doppler effect accompanying blood flow in a limb, and detects a blood volume and a blood flow in a blood vessel. 5. The vascular endothelial function measuring device according to claim 4, wherein the deriving means derives a change in a blood vessel area or a blood vessel diameter by dividing a blood flow detected by the blood flow detecting means by a blood flow velocity. 6. A blood pressure measuring means for measuring a blood pressure of the subject, wherein the deriving means derives a vascular endothelial function with reference to a change in blood pressure value before and after avascularization measured by the blood pressure measuring means. The vascular endothelial function measuring device according to any one of claims 1 to 4, characterized in that: 7. A pulse measuring unit for measuring a pulse rate, wherein the deriving unit is configured to calculate a pulse rate for one minute from a blood flow rate obtained from a bioelectrical impedance measured by the impedance measuring unit and a pulse rate measured by the pulse measuring unit. 7. The vascular endothelium according to claim 6, wherein the vascular endothelial function is derived from the blood flow volume before and after the avascularization and the peripheral vascular resistance by obtaining the volume of the output, calculating the peripheral vascular resistance from the obtained volume of the output per minute. Function measuring device. 8. A nitrogen oxide production amount detecting means for detecting a nitrogen oxide production amount in a blood vessel of a subject, and a vascular endothelium based on the nitrogen oxide production amount detected by the nitrogen oxide production amount detecting means. A deriving means for deriving a function, wherein the nitrogen oxide production amount detecting means detects a nitrogen oxide production amount by measuring a change in a blood vessel diameter before and after applying a mechanical stress to the blood vessel. Endothelial function measurement device. 9. The nitrogen oxide production amount detecting means utilizes a phenomenon in which the blood vessel is relaxed due to the production of nitrogen oxide to avascularize a blood vessel in a measurement range for a predetermined time, and to detect a blood vessel in a predetermined range before and after the avascularization. 9. The vascular endothelial function measuring apparatus according to claim 8, wherein the output of nitrogen oxide is estimated by measuring impedance. 10. The nitrogen oxide production amount detecting means further includes a blood flow detecting means for detecting a blood flow in the blood vessel, wherein a peripheral resistance value and a blood vessel diameter are calculated based on the measured bioimpedance value and intravascular flow value. 10. The method according to claim 9, wherein a maximum blood flow velocity and an average blood flow velocity are calculated, and a production amount of nitrogen oxide produced in the blood vessel is detected from a change rate of the blood vessel diameter.
The vascular endothelial function measuring device according to the above. 11. The deriving unit derives a vascular endothelial function based on a rate of an increase in the amount of nitrogen oxide every predetermined time after applying mechanical stress to a blood vessel detected by the nitrogen oxide production amount detecting unit. 9. The method according to claim 8, wherein
The vascular endothelial function measuring device according to any one of claims 10 to 10. 12. An avascularization means for advancing a blood vessel at a measurement site of a subject, an impedance measuring means for measuring a bioimpedance of the measurement site of the subject before and after the avascularization by the avascularization means, and the impedance Vasodilation change detection means for detecting a change in arterial vascular diameter of a predetermined portion of the subject before and after the avascularization by the avascularization means from the bioimpedance measured by the measurement means, and arterial vasodilation detected by the vasodilation change detection means A deriving unit for deriving a vascular endothelial function based on the change. 13. The blood vessel dilation change detecting means detects a peripheral arterial vasodilation change from a measured impedance fluctuation of the impedance measuring means, and detects a vascular resistance change in arterioles and capillaries from a basal impedance fluctuation. 13. The vascular endothelial function measuring device according to claim 12, wherein the device can be output to a deriving unit. 14. A pulse measuring device for measuring a pulse rate, wherein the vasodilatory change detecting device detects a blood volume obtained from a bioelectrical impedance measured by the impedance measuring device and a pulse rate measured by the pulse measuring device. The blood flow volume per minute is obtained, peripheral blood vessel resistance is obtained from the blood flow volume obtained per minute, and the vascular endothelial function is derived from the blood volume before and after the avascularization and the peripheral blood vessel resistance. Vascular endothelial function measurement device. 15. A blood flow detecting means for detecting a blood flow in a blood vessel, wherein a change in vascular dilatation of a peripheral artery before and after anastomosis by the avascularization means can be quantified. The vascular endothelial function measuring device according to any one of claims 12 to 14. 16. The blood flow detecting means transmits and receives an ultrasonic signal, detects a blood flow velocity by a Doppler effect accompanying a blood flow at a measurement site, and detects a blood volume and a blood flow in a blood vessel. 16. The expansion change detecting means according to claim 12, wherein a blood flow area or a blood vessel diameter change is derived by dividing a blood flow detected by the blood flow detecting means by a blood flow velocity. Vascular endothelial function measurement device.