Method and device for examining arterial blood vessel smooth muscle vasodilatory function

Abstract

Provided are a method and a device for examining arterial blood vessel smooth muscle vasodilatory function capable of examining smooth muscle function with a simple device without risk to the subject or requiring complicated exam preparation work.　The upper arm 14 is compressed using a cuff 12. During a preset arterial occlusion period T1, the artery is occluded, and the amplitude increase rate FR (%) of the amplitude F3 of the maximum amplitude volumetric pulse wave SM3 of the volumetric pulse waves successively obtained after the arterial occlusion period T1 with respect to the amplitude F2 of the volumetric pulse wave SM2 immediately after the arterial occlusion period T1 is calculated. On the basis of said amplitude increase rate FR (%), the smooth muscle vasodilatory function of an arterial blood vessel 14a is examined. As a result, there is no risk to the test subject because no drug is used, and since complicated exam preparation work requiring attendance by a physician, for example, is not required, and an ultrasound device for generating a cross-sectional image of the artery is not used, it is possible to examine smooth muscle function with a simple device.

Description

Method and device for testing smooth muscle diastolic function of arterial blood vessels

[0001] The present invention relates to an apparatus for testing smooth muscle function in arterial blood vessels based on a volume pulse wave obtained in synchronization with the pulsation of the arteries of a living body.

[0002] Prior to the onset of arteriosclerosis in the body, the function of endothelial cells on the surface of the intima of arterial blood vessels declines, followed by a decline in the function of the smooth muscle that makes up the media of arterial blood vessels. Therefore, by measuring these together, it is possible to accurately grasp the degree of progression of arteriosclerosis before morphological changes such as narrowing of arterial blood vessels or organ damage occur, enabling appropriate early intervention.

[0003] Endothelial function is evaluated by avascularization of the forearm, located distal to the site of arterial lumen diameter measurement (upper arm), for five minutes, creating an ischemic state in the area distal to the forearm. When the avascularization is released, blood flow resumes toward the ischemic distal area. The endothelial cells, stimulated by the blood flow (shear stress), produce nitric oxide (NO), which dilates the arterial blood vessels. Endothelial function is evaluated by the percentage increase in arterial lumen diameter, a flow-mediated vasodilation response. Measurement results are expressed as the percentage increase in arterial lumen diameter after avascularization, e.g., percent (% FMD), based on the baseline (pre-avascularization) vascular diameter obtained from the brachial artery using ultrasound cross-sectional images. Patent Document 1 describes an endothelial function testing device.

[0004] Smooth muscle function is evaluated by the degree of vasodilation response to nitroglycerin administration. As described in Non-Patent Documents 1 and 2, for example, in this case, the vascular diameter is expressed as the increase in vascular diameter after nitroglycerin administration, e.g., as a percentage (%NTG), based on the baseline vascular diameter (before nitroglycerin administration) obtained from an ultrasound cross-sectional image. In both endothelial function tests and smooth muscle function tests, the greater the numerical value of the increase in vascular diameter, the better the endothelial function and smooth muscle function are judged to be.

[0005] JP 2007-061182 A

[0006] "Heart" magazine 2014 Vol.46 No.10 Clinical laboratory journal "Medical Technology" 2006 Vol.34 No.1

[0007] However, the conventional smooth muscle function testing methods described above have the drawback of not only entailing risks to the subject but also requiring cumbersome test preparation work, such as preparing medication and arranging for a doctor to be present.

[0008] The present invention has been made against the background of the above circumstances, and its purpose is to provide a method and device for testing smooth muscle diastolic function of arterial blood vessels, which is risk-free for the subject, does not require complicated test preparation work, and can test smooth muscle function using simple equipment.

[0009] Based on the above background, the present inventors have conducted various studies and discovered the following phenomenon: after a relatively short period of compression at an arterial occlusion pressure using a cuff on a part of a living body, the amplitude of a cuff pulse wave (volume pulse wave), which is a pressure oscillation wave inside the cuff obtained from the compressed part of the living body, gradually increases and then decreases compared to the cuff pulse wave (base value) before or immediately after compression. In contrast to the occlusion period of approximately 5 minutes in Patent Document 1, which utilizes the flow-mediated dilation response of arterial blood vessels and results in a large change in blood flow velocity, in this case, the arterial occlusion period is a relatively short period of 30 seconds or less, during which the effect of NO production does not begin, there is little change in blood flow velocity after release from arterial occlusion, and vasodilation begins immediately after release from arterial occlusion. Therefore, this vasodilation phenomenon is presumed to be a myogenic response of smooth muscle at the compressed part, based on the relaxation response of smooth muscle after release of mechanical compression load, known as the Bayliss effect.

[0010] The method for testing smooth muscle diastolic function of an arterial blood vessel of the first invention was made based on the above findings, and the gist of the method is that it comprises: (a) a method for testing smooth muscle diastolic function of an arterial blood vessel in a part of a living body using a volume pulse wave generated from the part of the living body, (b) a compression step of compressing the part of the living body for a predetermined arterial occlusion period using a predetermined arterial occlusion pressure to occlude the arterial blood vessel in the part of the living body, and compressing the part of the living body with a predetermined pulse wave detection pressure that is sufficiently lower than the arterial occlusion pressure before, during, or after the arterial occlusion period; (c) an amplitude increase rate calculation step of calculating an amplitude increase rate of a volume pulse wave with a maximum amplitude among volume pulse waves sequentially obtained from the part of the living body after the arterial occlusion period, relative to the amplitude of a volume pulse wave obtained from the part of the living body immediately before or after the arterial occlusion period; and (d) a testing step of testing the smooth muscle diastolic function of the arterial blood vessel based on the amplitude increase rate.

[0011] The gist of a second invention for carrying out the above-mentioned method for testing smooth muscle diastolic function of arterial blood vessels is (a) an arterial blood vessel smooth muscle diastolic function testing device that tests smooth muscle diastolic function of an arterial blood vessel in a part of a living body using a volume pulse wave generated from the part of the living body, (b) a compression pressure control unit that occludes the arterial blood vessel in the part of the living body by compressing the part of the living body using a predetermined arterial occlusion pressure for a predetermined arterial occlusion period, and compresses the part of the living body with a predetermined pulse wave detection pressure that is sufficiently lower than the arterial occlusion pressure before, after, or after the arterial occlusion period; (c) an amplitude increase rate calculation unit that calculates an amplitude increase rate of a volume pulse wave with a maximum amplitude among volume pulse waves sequentially obtained from the part of the living body after the arterial occlusion period, relative to the amplitude of a volume pulse wave obtained from the part of the living body immediately before or after the arterial occlusion period; and (d) a smooth muscle diastolic function testing unit that tests the smooth muscle diastolic function of the arterial blood vessel based on the amplitude increase rate.

[0012] According to the method for testing smooth muscle diastolic function of an arterial blood vessel of the first invention, a part of a living body is compressed using a predetermined arterial occlusion pressure for a predetermined arterial occlusion period, thereby occluding the arterial blood vessel in the part of the living body, and before, during, or after the arterial occlusion period, the part of the living body is compressed using a predetermined pulse wave detection pressure that is sufficiently lower than the arterial occlusion pressure, and the amplitude increase rate of the maximum amplitude volume pulse wave among the volume pulse waves sequentially obtained after the arterial occlusion period is calculated relative to the amplitude of the volume pulse wave obtained from the part of the living body immediately before or after the arterial occlusion period after the arterial occlusion, and the smooth muscle diastolic function of the arterial blood vessel is tested based on the amplitude increase rate. This method does not involve the use of drugs, so there is no risk to the subject, does not require complicated test preparation work such as preparing drugs or arranging for a doctor to be present, and can test smooth muscle function with a simple device because it does not use an ultrasound device to generate cross-sectional images of the artery.

[0013] According to the second invention, the device for testing arterial smooth muscle diastolic function includes a compression pressure control unit that compresses a portion of the living body using a predetermined arterial occlusion pressure for a predetermined arterial occlusion period, thereby occluding the arterial blood vessel in the portion of the living body, a pulse wave detection pressure that is sufficiently lower than the arterial occlusion pressure before, during, or after the arterial occlusion period, a pulse wave detection unit that compresses the portion of the living body using a pulse wave detection pressure that is sufficiently lower than the arterial occlusion pressure, an amplitude increase rate calculation unit that calculates an amplitude increase rate of the maximum amplitude volume pulse wave among the volume pulse waves sequentially obtained from the portion of the living body after the arterial occlusion period, relative to the amplitude of a volume pulse wave obtained from the portion of the living body immediately before or after the arterial occlusion period, and a smooth muscle diastolic function testing unit that tests the smooth muscle diastolic function of the arterial blood vessel based on the amplitude increase rate. This method does not involve the use of drugs, poses no risk to the subject, does not require complicated test preparation work such as preparing drugs or arranging for a doctor to be present, and allows smooth muscle function to be tested with a simple device because it does not use an ultrasound device that generates cross-sectional images of the artery.

[0014] Preferably, the compression pressure control unit uses a cuff wrapped around the part of the living body to occlude the arterial blood vessels in the part of the living body by setting the compression pressure by the cuff to the arterial occlusion pressure that is sufficiently higher than the systolic blood pressure value of the living body, and maintains the compression pressure by the cuff at a pulse wave detection pressure that is lower than the diastolic blood pressure value of the living body, thereby collecting the volume pulse wave. In this way, the cuff is used not only to occlude the arterial blood vessels in the part of the living body but also to detect the volume pulse wave generated from the part of the living body, thereby simplifying the configuration of the smooth muscle diastolic function testing device.

[0015] Preferably, the compression pressure control unit sets the compression pressure on the part of the living body before the start of the arterial occlusion period to zero, and the amplitude increase rate calculation unit calculates the amplitude increase rate of the volume pulse wave with the largest amplitude among the volume pulse waves obtained sequentially after the arterial occlusion period has elapsed, relative to the amplitude of the volume pulse wave immediately after the arterial occlusion period, thereby making the calculation of the amplitude increase rate more accurate.

[0016] Preferably, the amplitude of the volume pulse wave is a value indicating the magnitude of the volume pulse wave immediately before a reflected wave component is superimposed on it. As a result, the value of the volume pulse wave immediately before a reflected wave component is superimposed on it is used as the amplitude of the volume pulse wave, thereby eliminating the influence of the reflected wave and enabling accurate calculation of the amplitude increase rate.

[0017] Preferably, the amplitude of the volume pulse wave is the amount of change in the pulse wave from a portion of the volume pulse wave corresponding to a peak in the first derivative waveform of the volume pulse wave to a portion of the volume pulse wave corresponding to a peak in the second derivative waveform of the volume pulse wave. As a result, the value of the volume pulse wave immediately before the reflected wave component is superimposed is used as the amplitude of the volume pulse wave, thereby excluding the influence of the reflected wave and enabling accurate calculation of the amplitude increase rate.

[0018] Preferably, the volume pulse wave is a pressure oscillation wave generated in the cuff when the compression pressure control unit maintains the cuff at a pulse wave detection pressure lower than the diastolic blood pressure of the living body. This allows the cuff to be used not only for occluding an arterial blood vessel in the part of the living body but also for detecting a volume pulse wave generated from the part of the living body, thereby simplifying the configuration of the smooth muscle diastolic function testing device.

[0019] Preferably, the arterial occlusion period is within the range of 10 to 30 seconds. This results in little change in blood flow velocity after the arterial occlusion period has elapsed, and arterial vascular dilation begins immediately after the arterial occlusion period has elapsed, thereby suppressing the influence of blood flow-dependent arterial vascular dilation and enabling accurate evaluation of arterial vascular smooth muscle dilation. If the arterial occlusion period exceeds 30 seconds, the influence of arterial vascular dilation due to NO production is mixed in, making it impossible to accurately evaluate arterial vascular smooth muscle dilation. Conversely, if the arterial occlusion period is less than 10 seconds, the arterial vascular smooth muscle dilation response is insufficient, making it impossible to accurately evaluate arterial vascular smooth muscle dilation.

[0020] 1 is a diagram illustrating an embodiment of an arterial smooth muscle diastolic function testing device according to the present invention; FIG. 2 is an enlarged view schematically illustrating the multilayer structure of the arterial blood vessel in the upper arm of FIG. 1; FIG. 3 is a time chart illustrating changes in cuff pressure controlled by a cuff pressure control unit included in the electronic control device in FIG. 1; FIG. 4 is a time chart illustrating the smooth muscle dilation response of the arterial blood vessel using changes in the lumen diameter of the arterial blood vessel obtained from an ultrasound cross-sectional image; FIG. 5 is a time chart illustrating the blood flow-mediated dilation response of the arterial blood vessel using changes in the lumen diameter of the arterial blood vessel obtained from an ultrasound cross-sectional image; FIG. 6 is a time chart illustrating the smooth muscle dilation response of the arterial blood vessel using changes in the amplitude of a cuff pulse wave; FIG. 7 is a flowchart illustrating the main parts of the control operation of the electronic control device of FIG. 1; FIG. 8 is a time chart illustrating the amplitude of a fixed rising section set within a reflected wave-free section of a volume pulse wave obtained immediately after release of arterial occlusion in the arterial blood vessel in another embodiment of the present invention; FIG. 9 is a time chart illustrating the amplitude of a fixed rising section of a volume pulse wave showing the maximum amplitude after release of arterial occlusion in another embodiment of the present invention; FIG. 10 is a time chart illustrating changes in the amplitude of a fixed rising section of a volume pulse wave obtained successively after release of arterial occlusion.

[0021] An embodiment of the present invention will be described in detail below with reference to the drawings. Note that in the following embodiment, the drawings are appropriately simplified or modified, and the dimensional ratios and shapes of the various parts are not necessarily drawn accurately.

[0022] FIG. 1 is a schematic diagram illustrating an apparatus 10 for testing arterial smooth muscle diastolic function, which is an example of the present invention. In FIG. 1, a cuff 12, which functions as a compression device, is a band-shaped inflatable bag wrapped around a part of a living body, such as an upper arm 14, similar to those used in blood pressure measurement. A piping 20 is connected to the cuff 12, and a cuff pressure control valve 16 and an air pump 18 are connected in series via the piping 20 to adjust the pressure or exhaust flow rate within the cuff 12 by supplying air to the cuff 12 and exhausting air from the cuff 12. A pressure sensor 22 is also connected to the cuff 12 via the piping 20, and a cuff pressure signal SPc for the arterial blood vessel 14a directly below the cuff 12 wrapped around the upper arm 14 is detected.

[0023] The cuff pressure signal SPc detected by the pressure sensor 22 is supplied to a low-pass filter 24 and a band-pass filter 26. The low-pass filter 24 separates the static pressure component from the cuff pressure signal SPc and outputs a signal representing the compression pressure Pc (mmHg). The band-pass filter 26 separates the volume pulse wave SM from the cuff pressure signal SPc by passing pressure vibration components that are synchronized with the patient's heartbeat and superimposed on the compression pressure Pc, and outputs a signal representing the volume pulse wave SM. The signals representing the compression pressure Pc and the volume pulse wave SM are input to an electronic control unit 30 via an A / D converter 28. The electronic control unit 30 is comprised of a so-called microcomputer, which processes input signals according to a pre-stored program and outputs the processing results to a display 32.

[0024] 2 is an enlarged view showing a schematic diagram of the multilayer structure of an arterial blood vessel 14a in the upper arm 14, which is the measurement target of the smooth muscle diastolic function testing device 10. This arterial blood vessel 14a has a three-layer structure including a tunica intima L1 having one layer of endothelial cells on its inner surface, a tunica media L2 made of smooth muscle and elastic fibers and having stretchability and elasticity, and a tunica adventitia L3 made of connective tissue.

[0025] The electronic control device 30 functionally comprises a cuff pressure control unit 34 , a volume pulse wave amplitude calculation unit 36 ​​, an amplitude increase rate calculation unit 42 , and a smooth muscle diastolic function testing unit 44 .

[0026] The cuff pressure control unit 34 functions as a compression pressure control unit for compressing the arterial blood vessel 14a in the upper arm 14, which is part of the living body, and when testing the smooth muscle expansion function of the arterial blood vessel 14a, it controls the compression pressure Pc of the cuff 12 using the cuff pressure control valve 16, for example, as shown in Figure 3. That is, upon startup of the smooth muscle diastolic function testing device 10 (at time t0), the compression pressure Pc is increased from 0 mmHg (atmospheric pressure) to a preset arterial occlusion pressure Pc1, and then the arterial occlusion pressure Pc1 is maintained for a preset arterial occlusion period T1, for example, within a range of approximately 10 to 30 seconds. When the arterial occlusion period T1 has elapsed (at time t1), the compression pressure Pc is reduced to a preset pulse wave detection pressure Pc2 by, for example, subtracting a predetermined pressure, for example, 10 mmHg, from the minimum blood pressure of the living body. This pulse wave detection pressure Pc2 is then maintained for a preset volume pulse wave detection period T2, for example, approximately 2 minutes. When the volume pulse wave detection period T2 has elapsed (at time t4), the compression pressure Pc is returned to 0 mmHg (atmospheric pressure).

[0027] The arterial occlusion pressure Pc1 is set to a pressure sufficient to occlude the arterial blood vessel 14a present in the part of the living body around which the cuff 12 is wrapped, i.e., the upper arm 14, for example, a pressure obtained by adding a predetermined pressure, for example, about 50 mmHg, to the systolic blood pressure of the living body. When the arterial blood vessel 14a is sufficiently occluded, the smooth muscle constituting the tunica media L2 of the arterial blood vessel 14a is also compressed. When this compression of the smooth muscle is released, the smooth muscle relaxes due to a myogenic response, and the amplitude of the volume pulse wave SM from the arterial blood vessel 14a increases.

[0028] The pulse wave detection pressure Pc2 is set to a pressure at which an undistorted volume pulse wave SM is obtained, for example, a pressure obtained by subtracting a predetermined pressure of approximately 10 mmHg from the diastolic blood pressure of the living body. The volume pulse wave detection period T2 during which this pulse wave detection pressure Pc2 is maintained is experimentally set in advance so as to sufficiently include the time t3 at which the volume pulse wave SM exhibiting the maximum amplitude due to the smooth muscle dilation response is generated among the volume pulse waves SM sequentially obtained after the arterial occlusion period T1.

[0029] The arterial occlusion period T1 is set within the maximum time period required for sufficient smooth muscle dilation and before flow-mediated dilation (FMD) resulting from NO production from endothelial cells due to shear stress occurs, for example, within a range of 10 to 30 seconds. For example, as shown in FIG. 4 (described later), in the myogenic response of the smooth muscle of the arterial blood vessel 14a (the smooth muscle relaxation response after the release of a mechanical compression load, known as the Bayliss effect), there is little change in blood flow velocity after the end of the arterial occlusion period T1, and arterial blood vessel dilation begins immediately after the end of the arterial occlusion period. Therefore, the arterial occlusion period T1 is set within a range of 10 to 30 seconds so that the influence of blood flow-dependent dilation of the arterial blood vessel 14a can be suppressed and smooth muscle dilation of the arterial blood vessel 14a can be accurately evaluated. According to experiments conducted by the inventors, when the arterial occlusion period T1 exceeds 30 seconds, the influence of arterial blood vessel dilation due to NO production becomes mixed in, making it impossible to accurately evaluate arterial blood vessel smooth muscle dilation. Conversely, when the arterial occlusion period T1 was less than 10 seconds, the dilation response of the smooth muscle of the arterial blood vessel 14a was insufficient, so that the dilation of the smooth muscle of the arterial blood vessel 14a could not be accurately evaluated.

[0030] (Test 1) The inventors conducted a test using an FMD measurement device (UNEXEF 38G) manufactured by Unex Corporation to measure the change in lumen diameter AD (mm) of the arterial blood vessel 14a and the blood flow velocity BV (cm / sec) after release of the arterial occlusion when the upper arm 14 of an adult male (55 years old) was occluded for an arterial occlusion period T1 (15 seconds). The change in lumen diameter AD of the arterial blood vessel 14a was measured from an ultrasonic cross-sectional image (long-axis image) displayed on the display of the FMD measurement device. The blood flow velocity BV was measured using an ultrasonic Doppler blood flow velocity sensor attached to the ultrasonic probe of the FMD measurement device. Figure 4 shows the test results. The lumen diameter AD of the arterial blood vessel 14a, shown by the curve in Figure 4, gradually increased from 3.9 mm after release of the arterial occlusion, reached a maximum value of 4.24 mm 75 seconds after release of the arterial occlusion, and then gradually decreased. The blood flow velocity BV shown by multiple points in Figure 4 is relatively flat within the range of 12 to 25 cm / sec, with no apparent tendency to change, although there is some variation. The arterial occlusion period T1 is set to be short so as not to cause a flow-mediated dilation response in the arterial blood vessel 14a, so the change in the diameter (mm) of the arterial blood vessel in Figure 4 is presumed to represent the smooth muscle dilation function.

[0031] (Test 2) The inventors also conducted a test using an FMD measurement device (UNEXEF 38G) manufactured by Unex Co., Ltd. to measure the change in the lumen diameter AD (mm) of the arterial blood vessel 14a and the blood flow velocity BV (cm / sec) after avascularization and release from avascularization when the forearm of an adult male (55 years old) was avascularized for a 5-minute period. As in Test 1, the change in the lumen diameter AD of the arterial blood vessel 14a was measured from an ultrasonic cross-sectional image (long-axis image) displayed on the display of the FMD measurement device. The blood flow velocity was also measured using an ultrasonic Doppler blood flow velocity sensor attached to the ultrasonic probe of the FMD measurement device. Figure 5 shows the test results. The lumen diameter AD of the arterial blood vessel 14a, shown by the curve in Figure 5, rapidly increased from 3.86 mm after avascularization and released 30 seconds later, reached a maximum value of 4.22 mm 44 seconds after avascularization and then gradually decreased. The blood flow velocity BV, indicated by multiple dots in Figure 5, is 75-80 cm / sec immediately after avascularization and release, but then exponentially decreases to about 25 cm / sec. This phenomenon indicates a typical flow-dependent dilation response of the arterial blood vessel 14a.

[0032] (Test 3) The inventors also conducted a test using the smooth muscle diastolic function testing device 10 shown in Figure 1 to measure changes in the amplitude F (difference from minimum to maximum) of the volume pulse wave MS obtained from the cuff after the upper arm of an adult male (55 years old) was occluded for an arterial occlusion period T1 (15 seconds). Figure 6 shows the test results. According to Figure 6, the amplitude F of the volume pulse wave gradually increases from a value F2 immediately after the arterial occlusion is released to a maximum value F3, after which it levels off or gradually decreases. According to Figure 6, the amplitude F of the volume pulse wave SM gradually increases from a value F2 immediately after the end of the arterial occlusion period to a maximum value F3, after which it saturates or gradually decreases.

[0033] Returning to FIG. 1 , the volume pulse wave amplitude calculation unit 36 ​​calculates and stores the amplitude F2 (mmHg) of the volume pulse wave SM2 obtained at the time of occurrence of the pulse wave SM several beats, e.g., the fifth beat, immediately after the arterial occlusion period T1 (time t2 in FIG. 3 ), among the volume pulse waves SM sequentially obtained during the volume pulse wave detection period T2 after the arterial occlusion period T1. The amplitude F3 (mmHg) of the volume pulse wave SM3 obtained at the time of occurrence of the volume pulse wave SM showing the maximum amplitude (time t3 in FIG. 3 ), among the volume pulse waves SM sequentially obtained during the volume pulse wave detection period T2 after the arterial occlusion period T1. The amplitude F2 is, for example, the difference (mmHg) between the minimum and maximum values ​​of the volume pulse wave SM2. The amplitude F3 is, for example, the difference (mmHg) between the minimum and maximum values ​​of the volume pulse wave SM3.

[0034] The amplitude increase rate calculation unit 42 calculates and stores the amplitude increase rate FR (%) of the amplitude F3 of the volume pulse wave SM3 relative to the amplitude F2 of the volume pulse wave SM2 using the amplitude F2 of the volume pulse wave SM2 and the amplitude F3 of the volume pulse wave SM3 according to the following equation (1): FR (%) = [(F3 - F2) / F2] × 100 (1)

[0035] Here, the vasodilation rate AR can be calculated for the following reason: According to Boyle's law, the product of the compression pressure Pc in the cuff 12 and the volume CV of the cuff 12 is constant (Pc × CV = constant), so when the volume of the arterial blood vessel 14a changes by ΔV, the volume CV of the cuff 12 changes by -ΔV, and the compression pressure Pc in the cuff 12 changes by ΔP, as shown in equation (2). (Pc + ΔP) × (CV - ΔV) = k ... (2)

[0036] Since ΔP×ΔV is minute, ignoring it, equation (2) can be expressed as equation (3), and substituting Pc×CV=k into equation (3) gives equation (4): Pc×CV+CV×ΔP-Pc×ΔV=k (3) ΔV=ΔP×(CV / Pc) (4)

[0037] Therefore, from equation (4), if the volume CV of the cuff 12 is constant and the compression pressure Pc of the cuff 12 is constant, ΔP, which is the magnitude (amplitude F) of the volume pulse wave SM, is proportional to the volume change ΔV of the arterial blood vessel 14a. From this, if we assume that the cross section of the arterial blood vessel 14a is circular, the amplitude increase rate FR in equation (1), which indicates the change in amplitude of the volume pulse wave SM, is a volume, and therefore the vasodilation rate AR of the arterial blood vessel 14a can be measured by using the square root of the amplitude increase rate FR.

[0038] The smooth muscle diastolic function testing unit 44 tests the smooth muscle diastolic function of the living body based on whether or not the amplitude increase rate FR (%) calculated by the amplitude increase rate calculation unit 42 exceeds a judgment threshold HFR that has been experimentally determined in advance. For example, if the amplitude increase rate FR (%) is equal to or greater than the judgment threshold HFR, the smooth muscle diastolic function of the living body is determined to be normal, but if the amplitude increase rate FR (%) is below the judgment threshold HFR, the smooth muscle diastolic function of the living body is determined to be impaired.

[0039] 7 is a flowchart illustrating the main control operations of the electronic control device 30. In FIG. 7, in response to the operation of an activation device (not shown), steps S1 to S9 (hereinafter, the term "step" will be omitted) corresponding to the cuff pressure control process executed by the cuff pressure control unit 34 are first executed. In S1, inflation of the cuff 14 wrapped around the upper arm 12 of the living subject is initiated, and the compression pressure Pc of the cuff 12 is increased. In the following S2, it is determined whether the compression pressure Pc of the cuff 12 has reached a preset arterial occlusion pressure Pc1. S2 is repeated as long as the determination in S2 is negative. If the determination is positive, in S3, the compression pressure Pc of the cuff 12 is maintained at the arterial occlusion pressure Pc1.

[0040] In S4, it is determined whether the time during which the compression pressure Pc of the cuff 12 is maintained at a preset arterial occlusion pressure Pc1 has elapsed, a preset arterial occlusion period T1, which is, for example, approximately 15 seconds. S4 is repeated as long as the determination in S4 is negative. If the determination is affirmative (time t1 in FIG. 3 ), the compression pressure Pc of the cuff 12 begins to decrease in S5. Next, in S6, it is determined whether the compression pressure Pc of the cuff 12 has reached a preset pulse wave detection pressure Pc2. S6 is repeated as long as the determination in S6 is negative. If the determination is affirmative, the compression pressure Pc of the cuff 12 is maintained at the pulse wave detection pressure Pc2 in S7. Next, in S8, the volume pulse wave SM is sequentially read while the compression pressure Pc of the cuff 12 is maintained at the pulse wave detection pressure Pc2 after the arterial occlusion period T1 has elapsed. In S9, it is determined whether the time during which the compression pressure Pc of the cuff 12 is maintained at a preset pulse wave detection pressure Pc2 has elapsed for a volume pulse wave detection period T2, which is preset, for example, about two minutes. As long as this determination is negative, S8 and S9 are repeated. If the determination is positive (time t4 in FIG. 3), S10 and subsequent steps are executed.

[0041] Next, steps S10 to S12 are executed, which correspond to the amplitude change rate calculation step executed by the amplitude change rate calculation unit 42. In S10, the amplitude F2 of the volume pulse wave SM2 obtained at the time of occurrence of the volume pulse wave SM (time t2 in FIG. 3 ) during the period in which the inside of the cuff 12 is stable immediately after the arterial occlusion period T1 has elapsed is calculated and stored, out of the volume pulse wave SM obtained sequentially during the volume pulse wave collection and detection period T2 after the arterial occlusion period T1. Next, in S11, the amplitude F3 of the volume pulse wave SM3 obtained at the time of occurrence of the volume pulse wave SM showing the maximum amplitude (time t3 in FIG. 3 ) is calculated and stored, out of the volume pulse waves SM obtained sequentially during the volume pulse wave detection period T2 after the arterial occlusion period T1. Then, in S12, the amplitude change rate (increase rate) FR (%) of the amplitude F3 of the volume pulse wave SM3 relative to the amplitude F2 of the volume pulse wave SM2 is calculated using the amplitude F2 of the volume pulse wave SM2 and the amplitude F3 of the volume pulse wave SM3 according to the following equation (1).

[0042] Then, in S13, which corresponds to the smooth muscle extension function testing process executed by the smooth muscle extension function testing unit 44, a test of the smooth muscle extension function of the living body is performed based on whether or not the amplitude increase rate FR (%) calculated in S12 exceeds a judgment threshold HFR that has been experimentally determined in advance and set, and the test results are displayed on the display 32.

[0043] As described above, the smooth muscle diastolic function testing method and the smooth muscle diastolic function testing device 10 of this embodiment include a cuff pressure control unit (compression pressure control unit) 34 that compresses the upper arm 14 to occlude the artery 14a for a preset arterial occlusion period T1 and then releases the compression of the cuff 12, and an amplitude control unit (amplitude control unit) 35 that calculates the amplitude increase rate FR of the amplitude F3 of the volume pulse wave SM3 with the maximum amplitude among the volume pulse waves sequentially obtained after the arterial occlusion period T1 has elapsed, relative to the amplitude F2 of the volume pulse wave SM2 obtained from the upper arm 14 after the arterial blood vessel 14a has been occluded immediately after the arterial occlusion period T1. The apparatus includes an increase rate calculation unit 42 and a smooth muscle diastolic function testing unit 44 that tests the smooth muscle diastolic function of the arterial blood vessel 14 a based on the amplitude increase rate FR, and the upper arm 14 is compressed using the cuff 12 to occlude the artery 14 a for a preset arterial occlusion period T1, and the amplitude increase rate FR (%) of the amplitude F3 of the maximum amplitude volume pulse wave SM3 among the volume pulse waves obtained sequentially after the arterial occlusion period T1 is calculated relative to the amplitude F2 of the volume pulse wave SM2 immediately after the arterial occlusion period T1, and the smooth muscle diastolic function of the arterial blood vessel 14 a is tested based on the amplitude increase rate FR (%). This method does not involve the use of drugs, so there is no risk to the subject, does not require complicated test preparation work such as the presence of a doctor, and can test smooth muscle function with a simple device because it does not use an ultrasound device that generates cross-sectional images of the artery.

[0044] Furthermore, according to the smooth muscle diastolic function testing device 10 of this embodiment, a cuff 12 is used as a compression device that is wrapped around the upper arm 14, which is a part of the living body, and the volume pulse wave SM is a pressure oscillation wave that is generated in the cuff 12 when the cuff 12 is maintained at a pulse wave detection pressure Pc2 that is lower than the diastolic blood pressure of the living body. As a result, the cuff 12 is used not only for occluding the artery in the upper arm 14 but also for detecting the volume pulse wave SM generated from the upper arm 14, and therefore the smooth muscle diastolic function testing device 10 can be easily configured.

[0045] According to the smooth muscle diastolic function testing device 10 of this embodiment, the cuff pressure control unit (compression pressure control unit) 34 sets the compression pressure on the upper arm 14 to zero before the start of the arterial occlusion period T1, and the amplitude increase rate calculation unit 42 calculates the amplitude increase rate FR of the amplitude F3 of the volume pulse wave SM3 with the largest amplitude among the volume pulse waves obtained sequentially during the pulse wave detection period T2 after the arterial occlusion period T1 has elapsed, relative to the amplitude F2 of the volume pulse wave SM2 immediately after the arterial occlusion period T1. This ensures accurate calculation of the amplitude increase rate FR.

[0046] Next, another embodiment of the present invention will be described. In the following description, parts common to the above embodiment will be designated by the same reference numerals and description thereof will be omitted.

[0047] Generally, reflected wave components from portions where the cross-sectional area is reduced, such as branches of the arterial blood vessel 14a, are superimposed on the waveform of the volume pulse wave SM. Therefore, strictly speaking, the amplitudes F2 and F3 are values ​​that include reflected wave components, and may be affected by variations in the reflected wave components.

[0048] For this reason, as shown in FIG. 1, the volume pulse wave amplitude calculation unit 36 ​​preferably includes a reflected wave sectionless calculation unit 38 that calculates a reflected wave sectionless Ar in which no reflected wave overlaps in the waveform of the volume pulse wave SM, for example, the volume pulse wave SM2, which is sequentially obtained after the arterial occlusion period T1, and a reflected wave sectionless amplitude calculation unit 40 that calculates the amplitude Fm (mmHg) in a certain rising section Am set within the reflected wave section Ar in the waveform of the volume pulse wave SM2.

[0049] As shown in FIG. 8 , the reflected wave section-free calculation unit 38 determines a portion of the waveform of the volume pulse wave SM2 obtained immediately after the arterial occlusion period T1 has elapsed, i.e., at the start of the volume pulse wave detection period T2, that corresponds to the maximum value of the first-order derivative waveform of the volume pulse wave SM2 (time t11 in FIG. 8 ). This portion is an inflection point of the volume pulse wave SM2, and reflected wave components may be superimposed after this inflection point. Next, the reflected wave section-free calculation unit 38 determines a portion of the waveform of the volume pulse wave SM2 that corresponds to the maximum value of the second-order derivative waveform of the volume pulse wave SM2 (time t10 in FIG. 8 ). This portion is an inflection point of the first-order derivative waveform of the volume pulse wave SM2, and is located near the rising point of the volume pulse wave SM2. The reflected wave section-free calculation unit 38 determines the period from time t10 near the rising point of the volume pulse wave SM2 to the inflection point (time t11) as the reflected wave section Ar. The constant rising section Am is set to be equal to the reflected wave non-section Ar of the volume pulse wave SM2 obtained at the start of the volume pulse wave detection period T2.

[0050] The reflected wave sectionless amplitude calculation unit 40 determines the amount of increase in the volume pulse wave SM2 within the fixed rising section Am as the amplitude F2m (mmHg) of the volume pulse wave SM2. Furthermore, for the volume pulse wave SM3 showing the maximum amplitude, as shown in Fig. 9 , the reflected wave sectionless amplitude calculation unit 40 determines the rising portion of the volume pulse wave SM3 corresponding to the maximum value of the second-order derivative waveform of the volume pulse wave SM3 (time t20 in Fig. 9 ), and determines the amount of increase in the volume pulse wave SM3 from the rising portion to the end of the fixed rising section Am (time t21 in Fig. 9 ) as the amplitude F3m (mmHg) of the volume pulse wave SM3. At time t21 in Fig. 9 , the reflected wave sectionless Ar has increased and is greater than the value of the fixed rising section Am. 9, the inflection point corresponding to the maximum value of the first derivative waveform of the volume pulse wave SM3 is indicated by a dashed line, and for reference, the inflection point of the waveform of the volume pulse wave SM3 showing the maximum amplitude is shown to exceed the end (time t21) of the constant rising section Am, which is set within the reflected wave non-section Ar.

[0051] The amplitude change rate calculation unit 42 of this embodiment uses the amplitude F2m of the volume pulse wave SM2 and the amplitude F3m of the volume pulse wave SM3 to calculate and store the amplitude increase rate FRm (%) of the amplitude F3m of the volume pulse wave SM3 relative to the amplitude F2m of the volume pulse wave SM2 from equation (1) as follows: FRm (%) = [(F3m - F2m) / F2m] x 100

[0052] The smooth muscle diastolic function testing unit 44 tests the smooth muscle diastolic function of the living body based on whether or not the amplitude increase rate FRm (%) calculated by the amplitude increase rate calculation unit 42 exceeds a judgment threshold HFRm that is experimentally determined in advance. For example, if the amplitude increase rate FRm (%) is equal to or greater than the judgment threshold HFRm, it is determined that the smooth muscle diastolic function of the living body is normal, but if the amplitude increase rate FRm (%) is below the judgment threshold HFRm, it is determined that the smooth muscle diastolic function of the living body has decreased.

[0053] (Test 4) Figure 10 shows the change in amplitude Fm of the constant rising section Am of the volume pulse wave SM superimposed on the compression pressure Pc of the cuff 12 wrapped around the upper arm 14 after the release of the arterial occlusion, when the upper arm 14 of an adult male (55 years old) was occluded for an arterial occlusion period T1 (15 seconds), as in Figure 6 . As shown in Figure 10, the amplitude Fm of the constant rising section Am of the volume pulse wave SN gradually increases from the amplitude F2m of the constant rising section Am immediately after the arterial occlusion period T1, reaches a maximum amplitude F3m at time t3, approximately 40 seconds after the arterial occlusion period T1, and then remains flat. The maximum amplitude F3m may be a saturated value. The amplitude F2m of the constant rising section Am at time t2 immediately after the arterial occlusion period T1 and the maximum amplitude F3m of the constant rising section Am at time t3 are preferably averaged over a predetermined number of adjacent data points.

[0054] In addition to the same effects as those of the above-described first embodiment, the second embodiment also provides the following effect. That is, according to the smooth muscle diastolic function testing device 10 of the second embodiment, the amplitude F2m of the volume pulse wave SM2 is a value indicating the magnitude of the volume pulse wave SM2 immediately before the reflected wave component is superimposed. As a result, the value of the volume pulse wave SM2m immediately before the reflected wave component is superimposed is used as the amplitude Fm of the volume pulse wave SM2m, thereby eliminating the influence of the reflected wave and enabling accurate calculation of the amplitude increase rate FRm.

[0055] Furthermore, according to the smooth muscle diastolic function testing device 10 of the second embodiment, the amplitude F2m of the volume pulse wave SM2m is the amount of increase from a portion of the volume pulse wave SM2 corresponding to the peak of the first-order derivative waveform of the volume pulse wave SM2 (at time t10) to a portion of the volume pulse wave SM2 corresponding to the peak of the second-order derivative waveform of the volume pulse wave SM2 (at time t11). As a result, the value of the volume pulse wave SM2 immediately before the reflected wave component is superimposed is used as the amplitude F2m of the volume pulse wave SM2, eliminating the influence of the reflected wave and allowing for accurate calculation of the amplitude increase rate FRm.

[0056] Although one embodiment of the present invention has been described above with reference to the drawings, the present invention can also be applied to other embodiments.

[0057] For example, in the first and second embodiments, the cuff 12 is wrapped around the upper arm 14 as a part of the living body, but it may be wrapped around another part of the living body such as the forearm or the lower leg.

[0058] In addition, in the above-mentioned first and second embodiments, air, which is a compressed fluid, is supplied to the cuff 12 to generate the compression pressure Pc, but instead, an incompressible fluid such as water or oil may be used.

[0059] Furthermore, in the above-described second embodiment, the amplitude Fm of the volume pulse wave SM was the difference between the value of the portion of the volume pulse wave SM corresponding to the peak of the first derivative waveform and the value of the portion of the volume pulse wave SM corresponding to the peak of the second derivative waveform, but it may also be the difference between the value of the portion of the volume pulse wave SM corresponding to the peak of the first derivative waveform and the rising point (minimum value) of the volume pulse wave SM.

[0060] In the first and second embodiments, the cuff 12 made up of an inflatable bag is used as the compression device for compressing the upper arm 14. However, a belt wrapped around the upper arm 14 may also be used. In this case, the belt preferably includes an actuator for adjusting the belt tension. In this case, the pressure sensor is inserted between the belt and the upper arm 14.

[0061] In the above-described first and second embodiments, the amplitude increase rate FR of the amplitude F3 of the volume pulse wave SM3 having the maximum amplitude among the volume pulse waves obtained sequentially after the arterial occlusion period T1 is calculated relative to the amplitude F2 of the volume pulse wave SM2 immediately after the arterial occlusion period T1, but the amplitude increase rate FR of the amplitude F3 of the volume pulse wave SM3 having the maximum amplitude among the volume pulse waves obtained sequentially after the arterial occlusion period T1 may be calculated relative to the amplitude F2 of the volume pulse wave SM2 immediately before the arterial occlusion period T1. In this case, the compression pressure Pc of the cuff 12 immediately before the arterial occlusion period T1 is used as the pulse wave detection pressure Pc2.

[0062] Although the preferred embodiment of the present invention has been described in detail above with reference to the drawings, the present invention is not limited to this and may be implemented with various modifications within the scope of the spirit of the present invention.

[0063] 10: smooth muscle diastolic function testing device, 12: cuff (compression device), 14: upper arm, 14a: arterial blood vessel, 30: electronic control device, 34: cuff pressure control unit (compression pressure control unit), 36: volume pulse wave amplitude calculation unit, 38: reflected wave no section calculation unit, 40: reflected wave no section amplitude calculation unit, 42: amplitude change rate calculation unit, 44: smooth muscle diastolic function testing unit, L2: tunica media (smooth muscle), SM: volume pulse wave, SM2: volume pulse wave obtained at time t2, F2: amplitude of volume pulse wave obtained at time t2, SM3: amplitude of volume pulse wave obtained at time t3 F3: amplitude of the volume pulse wave obtained at time t3, FR: amplitude increase rate, HFR: judgment threshold, SPc: cuff pressure signal, Pc: compression pressure, Pc1: arterial occlusion pressure, Pc2: pulse wave detection pressure, T1: arterial occlusion period, T2: volume pulse wave detection period, Fm: amplitude of a constant rising section Am of the volume pulse wave, F2m: amplitude of a constant rising section Am of the volume pulse wave SM2 obtained at time t2, F3m: amplitude of a constant rising section Am of the volume pulse wave SM3 obtained at time t3, FRm: amplitude increase rate

Claims

1. A method for testing smooth muscle diastolic function of an arterial blood vessel in a part of a living body, using a volume pulse wave generated from the part of the living body, comprising: a compression step of compressing the part of the living body for a preset arterial occlusion period using a preset arterial occlusion pressure to occlude the arterial blood vessel in the part of the living body, and compressing the part of the living body with a preset pulse wave detection pressure sufficiently lower than the arterial occlusion pressure before, during or after the arterial occlusion period; an amplitude increase rate calculation step of calculating an amplitude increase rate of a volume pulse wave with a maximum amplitude among volume pulse waves sequentially obtained from the part of the living body after the arterial occlusion period, relative to the amplitude of a volume pulse wave obtained from the part of the living body immediately before or after the arterial occlusion period; and an examination step of testing the smooth muscle diastolic function of the arterial blood vessel based on the amplitude increase rate.

2. An arterial vascular smooth muscle diastolic function testing device for testing smooth muscle diastolic function of an arterial blood vessel within a part of a living body using a volume pulse wave generated from the part of the living body, comprising: a compression pressure control unit for compressing the part of the living body for a preset arterial occlusion period using a preset arterial occlusion pressure to occlude the arterial blood vessel within the part of the living body, and for compressing the part of the living body with a preset pulse wave detection pressure sufficiently lower than the arterial occlusion pressure before, during or after the arterial occlusion period; an amplitude increase rate calculation unit for calculating an amplitude increase rate of a volume pulse wave with a maximum amplitude among volume pulse waves sequentially obtained from the part of the living body after the arterial occlusion period, relative to the amplitude of a volume pulse wave obtained from the part of the living body immediately before or after the arterial occlusion period; and a smooth muscle diastolic function testing unit for testing the smooth muscle diastolic function of the arterial blood vessel based on the amplitude increase rate.

3. The smooth muscle extension function testing device of claim 2, characterized in that the compression pressure control unit uses a cuff wrapped around a part of the living body to occlude an arterial blood vessel in the part of the living body by setting the compression pressure of the cuff to the arterial occlusion pressure, and collects the volume pulse wave by maintaining the compression pressure of the cuff at a pulse wave detection pressure.

4. The smooth muscle extension function testing device of claim 2, characterized in that the compression pressure control unit sets the compression pressure on the part of the living body before the start of the arterial occlusion period to zero, and the amplitude increase rate calculation unit calculates the amplitude increase rate of the volume pulse wave with the maximum amplitude among the volume pulse waves obtained sequentially after the arterial occlusion period has elapsed, relative to the amplitude of the volume pulse wave immediately after the arterial occlusion period.

5. The smooth muscle expansion function testing device according to claim 2, characterized in that the amplitude of the volume pulse wave is a value indicating the magnitude of the volume pulse wave immediately before a reflected wave component is superimposed thereon.

6. The smooth muscle expansion function testing device of claim 2, characterized in that the amplitude of the volume pulse wave is the amount of change in the pulse wave from a portion of the volume pulse wave corresponding to a peak of the first derivative waveform of the volume pulse wave to a portion of the volume pulse wave corresponding to a peak of the second derivative waveform of the volume pulse wave.

7. The smooth muscle expansion function testing device of claim 3, characterized in that the volume pulse wave is a pressure vibration wave generated in the cuff when the compression pressure control unit maintains the cuff at a pulse wave detection pressure lower than the minimum blood pressure of the living body.

8. The smooth muscle diastolic function testing device according to claim 2, wherein the arterial occlusion period is within a range of 10 to 30 seconds.

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