Patent Application
20160271417
This disclosure relates to a device that treats carbon monoxide poisoning, the device being used to treat a patient suffering from carbon monoxide poisoning, and an upper clothing and a catheter that include the device that treats carbon monoxide poisoning.
Carbon monoxide poisoning occurs when carbon monoxide, which is, for example, produced by incomplete combustion occurring such as in fires, is inhaled. Thus, carbon monoxide poisoning is not region specific and can occur in any region. About over 2,000 of deaths per year are attributed to carbon monoxide poisoning in Japan. It is said that at least tens of thousands of people exhibit no symptoms of the poisoning, but potentially suffer from carbon monoxide poisoning in Japan.
Inhaled carbon monoxide binds to hemoglobin in blood to form carbon monoxide-hemoglobin (CO-Hb). The affinity of carbon monoxide for hemoglobin is known to be about 250-fold higher than the affinity of oxygen for hemoglobin. Thus, inhaled carbon monoxide inhibits the binding of oxygen to hemoglobin to form oxyhemoglobin (O2-Hb). CO-Hb also inhibits the release of oxygen from O2-Hb in peripheral tissues. Thus, inhaled carbon monoxide reduces the oxygen-carrying capacity of hemoglobin and induces tissue hypoxia (see, for example, E. Narimatsu, Y. Asai, “2. Carbon Monoxide Poisoning,” Clinic All-Round an extra issue, 2002.5, Vol. 51, pp. 748-751).
As initial therapy for carbon monoxide poisoning, it is effective to immediately remove carbon monoxide from the body by oxygen administration. Methods of administering oxygen to a patient suffering from carbon monoxide poisoning include use of normal breathing to administer oxygen, breathing in concentrated oxygen (for example, 100% oxygen at 1 atmosphere), and hyperbaric oxygen therapy (for example, breathing in 100% oxygen at 2 atmosphere). When the effects of the respective methods of administering oxygen in removing carbon monoxide are compared for half-life of carbon monoxide in blood, the half-life of carbon monoxide is 4 hours in normal breathing, the half-life of carbon monoxide is 40 minutes in breathing in concentrated oxygen, and the half-life of carbon monoxide is 23 minutes in hyperbaric oxygen therapy (see K. Iseki, C. Tase, “Treatment of Acute Poisoning,” Japanese Journal of Intensive Care Medicine, 2002, 26 (5), pp. 329-333). This shows that hyperbaric oxygen therapy is very effective in treating carbon monoxide poisoning.
As an alternative to donor blood, a hemoglobin-based artificial oxygen carrier is known (see, for example, Japanese Unexamined Patent Application Publication No. 2007-045718). The artificial oxygen carrier is stored with carbon monoxide bound thereto. The artificial oxygen carrier having carbon monoxide bound thereto is stable in air and thus can be stored for a long period of time. The carbon monoxide is dissociated by exposure to visible light, and the carbon monoxide is replaced by oxygen by binding oxygen to the oxygen carrier to obtain an artificial oxygen carrier having oxygen bound thereto.
Hyperbaric oxygen therapy requires administration of highly concentrated oxygen (100% oxygen) under a high atmosphere environment (at 2 atmosphere) and, thus, the therapy is performed by using a large hyperbaric oxygen therapy chamber. However, the hyperbaric oxygen therapy chamber is expensive and requires operation by a doctor, a nurse, and a technician, and thus only about 50 medical facilities have the chamber in Japan. Thus, it is very difficult to promptly provide appropriate initial therapy to patients suffering from carbon monoxide poisoning throughout the country.
It could therefore be helpful to provide a device that treats carbon monoxide poisoning, the device allowing medical facilities in various regions to use the cheaper device to provide effective initial therapy for patients suffering from carbon monoxide poisoning, and an upper clothing and a catheter that includes the device that treats carbon monoxide poisoning.
As described above, carbon monoxide binding to a hemoglobin-based artificial oxygen carrier is dissociated by exposure to visible light. This suggests that light exposure may also result in dissociation of carbon monoxide from CO-Hb in patients suffering from carbon monoxide poisoning. We found that exposure of CO-Hb of rats to light resulted in dissociation of carbon monoxide from the CO-Hb. We believe that exposure of blood of patients suffering from carbon monoxide poisoning to light can result in dissociation of carbon monoxide from the CO-Hb. However, hemoglobin has high affinity for carbon monoxide as described above, and thus even if carbon monoxide is dissociated in blood, the carbon monoxide may bind to the hemoglobin again before oxygen binds to the hemoglobin.
We also found that it is effective to directly or indirectly expose blood to light immediately before the blood flows into lung.
We thus provide:
We provide effective and inexpensive initial therapy for patients suffering from carbon monoxide poisoning in any location.
Our device that treats carbon monoxide poisoning will be described with reference to the accompanying drawings. The device that treats carbon monoxide poisoning includes a light emitter that emits light having a wavelength of 600 to 750 nm. The device is mainly used for treatment of a patient suffering from acute carbon monoxide poisoning and exposes blood flowing through the pulmonary artery to a light having a predetermined wavelength. In Examples 1 and 2, a catheter that includes the device that treats carbon monoxide poisoning will be described, while in Example 3, an upper clothing that includes the device that treats carbon monoxide poisoning will be described.
A catheter will be described in detail with reference to the accompanying drawings. The catheter is for insertion into a blood vessel of a patient suffering from carbon monoxide poisoning and for exposure of the blood to light and can be inserted in a manner similar to pulmonary artery catheters. For example, the distal end of the catheter is inserted through the right internal jugular vein and is advanced to the superior vena cava, the right atrium, the right ventricle, and the pulmonary artery. Then, the distal end of the catheter is deployed adjacent to the pulmonary artery and exposes the blood flowing through the pulmonary artery to light having a predetermined wavelength.
As illustrated in
The catheter body 120 is an elongated tube that is partially inserted into a blood vessel to connect the inside of the blood vessel to the outside of the blood vessel. The catheter body 120 includes a distal end portion 121, a first lumen 122, a second lumen 123, and a third lumen 124. The catheter body 120 is curved with a predetermined radius of curvature as shown in
The distal end portion 121 is a distal end region of the catheter body 120. The distal end portion 121 includes a light transmitting portion 143 of the light emitter 140 that emits light having a predetermined wavelength. The distal end portion 121 is a portion from the distal end of the catheter body 120 to a position at 10 to 15 cm from the distal end.
The material of the distal end portion 121 is not restricted as long as the material can transmit light having a predetermined wavelength. The material of the distal end portion 121 is, for example, polyvinyl chloride or polyurethane resin. The entire portion of the catheter body 120, including the distal end portion 121, are formed of light-transmissive polyvinyl chloride or polyurethane resin. Thus, the entire portion of the catheter body 120, including the distal end portion 121, preferably have a softness (flexibility) that allows the portions to bend enough to pass through the right internal jugular vein to the pulmonary artery.
The size and the shape of the radial cross-section of the first lumen 122, the second lumen 123, and the third lumen 124 are not restricted. The radial cross-section of the first lumen 122, the second lumen 123, and the third lumen 124 has a size that is about one third of the size of the radial cross-section of the catheter body 120. The radial cross-section of the first lumen 122, the second lumen 123, and the third lumen 124 has a shape of a sector that is one third of a circle.
The first lumen 122 includes a light guide 141. The distal end of the first lumen 122 in the catheter body 120 is closed. This prevents the blood from flowing into the first lumen 122.
The second lumen 123 is a pathway for gas supplied to the balloon 160. The second lumen 123 is in communication with the balloon 160 via a through-hole 126 disposed in the inner wall of the second lumen 123. The distal end of the second lumen 123 in the catheter body 120 is also closed. This prevents the blood from flowing into the second lumen 123.
The third lumen 124 includes a cable 127 connected to the pressure sensor 180. In the distal end of the third lumen 124, the pressure sensor 180 is incorporated. The distal end of the third lumen 124 in the catheter body 120 is also closed. This prevents the blood from flowing into the third lumen 124.
To the proximal end of the catheter body 120, a light guide lumen 131, a balloon lumen 132, and a pressure sensor lumen 133 are connected via a connector 130. The light guide lumen 131, the balloon lumen 132, and the pressure sensor lumen 133 are a hollow tube.
The light guide lumen 131 includes the light guide 141. One end of the light guide lumen 131 is connected to the first lumen 122 via the connector 130, and the other end is connected to a light source connector 134. The light source connector 134 optically connects the light guide 141 to a light source 142.
The balloon lumen 132 is a pathway for gas supplied to the balloon 160. One end of the balloon lumen 132 is connected to the second lumen 123 via the connector 130, and the other end is connected to a balloon inflation valve 135. The balloon inflation valve 135 can be connected only to a syringe 136 having a volume that corresponds to the volume of gas supplied to the balloon 160.
The pressure sensor lumen 133 includes the cable 127 connected to the pressure sensor 180. One end of the pressure sensor lumen 133 is connected to the third lumen 124 via the connector 130, and the other end is connected to a connector 137 connected to a monitor (not shown). The connector 137 electrically connects the cable 127 to the monitor.
The light emitter 140 transmits light through the inside to the outside of the catheter body 120 in the distal end portion 121 (at the distal end) of the catheter body 120. As described below, the catheter 100 is used by deploying the distal end of the catheter body 120 in blood. If heat was generated in the portion deployed in a blood vessel, the blood components might be modified. Thus, the portion of the catheter 100 to be deployed in a blood vessel preferably generates no heat. The structure of the light emitter 140 is not restricted as long as the portion of the catheter 100 to be deployed in a blood vessel generates no heat. The light emitter 140 includes the light guide 141 and the light source 142.
The light guide 141 allows light emitted by the light source 142 to enter from one end and allows the light to exit from the distal end in the distal end portion 121. The light guide 141 extends in the first lumen 122, the connector 130, and the light guide lumen 131 of the catheter body 120. The light guide 141 serves the above functions and preferably has a softness that allows the guide to bend enough to pass through the right internal jugular vein to the pulmonary artery during use. Examples of the light guide 141 include optical fibers and silica fibers. The light guide 141 is an optical fiber, and the light transmitting portion 143 of the light guide 141 is disposed at the distal end of the catheter body 120 as shown in
We conducted studies to find a wavelength of light that should be transmitted through the light transmitting portion 143 (distal end) of the light guide 141. Transmission of light in biological tissues (medium) containing CO-Hb, O2-Hb, Hb, and water as absorbers was analyzed by the Monte Carlo method. For scattering coefficients, we referred to Steven L Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58, 2013, pp. R37-R61. For absorption coefficient, we referred to W. G. Zijlstra, A. Buursma, O. W. Van Assendelft, Visible and near infrared absorption spectra of human and animal Haemoglobin determination and application, 2000, pp. 58-59 and W. G. Zijistra, A. Buursms, W. P. Meeuwsen, “Absorption Spectra of Human Fetal and Adult Oxyhemoglobin, De-Oxyhemoglobin, Carboxyhemoglobin, and Methemoglobin,” CLINICAL CHEMISTRY, Vol. 37, 9, 1991, pp. 1633-1638. The results of the analysis by the Monte Carlo method are shown in
As illustrates in
To allow CO-Hb to absorb more light energy, the light should have somewhat high susceptibility to absorption by CO-Hb. The wavelength of light having somewhat high susceptibility to absorption by CO-Hb was derived from earlier studies reported in literature. We found that light having a wavelength of 750 nm or more is less susceptible to absorption by CO-Hb and that sufficient energy is not transferred. These indicate that the appropriate wavelength of light that allows light energy to be transferred widely and to be efficiently absorbed by CO-Hb is 600 to 750 nm. By way of example, light having a wavelength of 680 nm was used in experiments described below, because the light has a penetration depth of from 1 to 2 mm and an absorption coefficient of about 0.01/mm and is expected to act on blood located relatively deep. As described above, light having a wavelength of 600 to 750 nm can effectively dissociate carbon monoxide from CO-Hb (carbon monoxide-hemoglobin). Thus, the light transmitted through the light transmitting portion 143 (distal end) of the light guide 141 preferably has a wavelength of 600 to 750 nm.
The type of the light source 142 is not restricted. Examples of the light source 142 include LEDs and cold lamps. The light emitted by the light source 142 enters from a surface of the proximal end of the light guide 141, then the light is guided within the light guide 141, and the light exits from the light transmitting portion 143. The light emitted by the light source 142 may have any illuminance at blood to be exposed as long as the light can dissociate carbon monoxide from CO-Hb. The blood is preferably exposed to light at an illuminance of 100,000 lux or more. If the blood was exposed to light at an illuminance of less than 100,000 lux, carbon monoxide might not be dissociated from CO-Hb. The light transmitted through the light transmitting portion 143 preferably has an intensity that does not affect the living body. In particular, the light transmitted through the light transmitting portion 143 preferably has an intensity of 1 mW or more. If the light transmitted through the light transmitting portion 143 had an intensity of less than 1 mW, carbon monoxide might not be dissociated from CO-Hb.
The balloon 160 guides the distal end of the catheter body 120 to downstream blood flow. The balloon 160 is disposed around part of a circumferential surface of the distal end portion of the catheter body 120. The volume of the balloon 160 is not restricted and usually about 0.7 mL to 1.5 mL. The material of the balloon 160 is not restricted and usually natural rubber or the like. When the plunger of the syringe 136 is pushed, the gas in the syringe 136 is allowed to flow through the balloon lumen 132, the connector 130, and the second lumen 123 into the balloon 160 to inflate the balloon 160.
The pressure sensor 180 is disposed at the distal end of the distal end portion 121 and detects intracardiac or intravascular pressure to provide an indication of the location of the distal end of the catheter 100. The pressure sensor 180 connects to the cable 127.
We found that exposure of CO-Hb to light having a predetermined wavelength can result in effective dissociation of carbon monoxide from CO-Hb. In the living body, the blood flows through the right atrium into the heart and flows through the right ventricle into the lung. The lung exchanges carbon dioxide in the blood from the heart and inhaled oxygen. Thus, we assumed that dissociation of carbon monoxide from CO-Hb immediately before the blood enters the lung could result in efficient removal of carbon monoxide from the body of a patient suffering from acute carbon monoxide poisoning using the functions of the lung. However, strong light delivered from outside the body cannot be efficiently transmitted to the blood before the blood flows into the lung. Thus, it is necessary that the light transmitting portion 143 that transmits light be disposed within the body. Use of the catheter 100 that allows the light transmitting portion 143 to be inserted into the pulmonary artery just proximal to the lung provides effective removal of carbon monoxide.
The catheter 100 can be used, for example, in the following manner. The catheter 100 is a pulmonary artery catheter, and thus is inserted from, for example, the right internal jugular vein. First, local anesthesia is provided to a site for insertion of the catheter 100. Next, a guide wire is inserted into the blood vessel, and then the catheter 100 is inserted over the guide wire. After the catheter 100 is inserted a predetermined distance, the balloon 160 is inflated. The catheter 100 is inserted while monitoring the intravascular or intracardiac pressure using the pressure sensor 180 disposed at the distal end of the catheter body 120. The balloon 160 travels through the blood stream, which allows the distal end of the catheter 100 to advance through the right atrium, the right ventricle, and the pulmonary artery. Preferably, the distal end of the catheter 100 is deployed adjacent to the alveoli. The light having a wavelength in the range of from 600 to 750 nm is transmitted through the light transmitting portion 143, leaving the distal end of the catheter 100 indwelling in a predetermined location. The light transmitting time is not restricted. The light transmitting time is adjusted depending on the symptoms of the patient and the concentration of carbon monoxide in blood.
Although the light transmitting portion 143 is disposed at a distal-end side of the catheter body 120, the light transmitting portion 143 may be disposed in a proximal-end side of the catheter body 120, the side being proximal from the balloon 160 (
Although, use of an optical fiber and the light source 142 as the light emitter 140 is described by way of example, an LED may be disposed at the distal end of the catheter body 120 as the light emitter 140, as illustrated in
A catheter 200 according to Example 2 differs from the catheter 100 according to Example 1 in, for example, the structure of a catheter body 220. Similar reference numerals are used to denote components similar to the components of the catheter 100 according to Example 1, and the components are not described here.
As illustrated in
The first lumen 222 includes the plurality of light guides 141. The proximal end of the plurality of light guides 141 is optically connected to a light source 142. As illustrated in
As illustrated in
Now, an upper clothing will be described with reference to the accompanying drawings. The upper clothing is an upper clothing that subjects a patient suffering from carbon monoxide poisoning to light radiation to treat the carbon monoxide poisoning and can be worn in a similar manner to clothing such as vests, shirts, and sweaters. Thus, the upper clothing transmits light having a predetermined wavelength to the entire pulmonary vascular bed that allows for gas exchange with air outside the body, when the patient wears the clothing. Preferably, the upper clothing is put directly on the body to transmit light to the blood in the blood vessel.
As illustrated in
The front body 320 is positioned on the stomach side (front side), as seen by a wearer, when the clothing is worn. The front body 320 includes the first light emitter 362 and the second light emitter 364. The configuration of the front body 320 is not restricted. The front body 320 may or may not include left and right bodies. The front body 320 includes left and right bodies, which are a first front body 322 and a second front body 324. The first front body 322 and the second front body 324 are configured to connect to each other by a zipper 380. This makes the upper clothing 300 easy to put on and take off. The first front body 322 is positioned on the left side when the clothing is worn. The first front body 322 includes the first light emitter 362. The second front body 324 is positioned on the right side when the clothing is worn. The second front body 324 includes the second light emitter 364.
The back body 340 is positioned on the back side, as seen by a wearer, when the clothing is worn. The back body 340 includes the third light emitter 366.
The light emitters 360 emit light toward the entire chest on the inside of the upper clothing 300. The light emitters 360 include the first light emitter 362, the second light emitter 364, and the third light emitter 366. As described below, the upper clothing 300 is worn by a patient during use. If the light transmitting portions generated heat, the wearer would be burned, and thus the portions that face the wearer preferably generate no heat. The configuration of the first light emitter 362, the second light emitter 364, and the third light emitter 366 is not restricted as long as the portions that face the wearer generate no heat. The first light emitter 362 includes a plurality of first light guides 368 and a first light source 370. The second light emitter 364 includes a plurality of second light guides 372 and a second light source 374. The third light emitter 366 includes a plurality of third light guides 376 and a third light source 378.
The first light guides 368, the second light guide 372, and the third light guides 376 allow light respectively emitted by the first light source 370, the second light source 374, and the third light source 378 disposed outside of the front body 320 and the back body 340 to enter from one end and allow the light to exit from the distal end on the inside of the upper clothing 300. The first light guides 368, the second light guides 372, and the third light guides 376 are disposed on the inside of the upper clothing 300. Preferably, the first light guides 368, the second light guides 372, and the third light guides 376 serve the above functions and preferably have an appropriate softness. Examples of the first light guides 368, the second light guides 372, and the third light guides 376 include optical fibers and silica fibers. The first light guides 368, the second light guides 372, and the third light guides 376 are an optical fiber. There may be a single first light guide 368, a single second light guide 372, and a single third light guides 376 as long as the guides achieve a desired illuminance of transmitted light as described below. The first light guides 368 are disposed on the inside of the first front body 322, the second light guides 372 are disposed on the inside of the second front body 324, and the third light guides 376 are disposed on the inside of the back body 340. The first light guides 368, the second light guides 372, and the third light guides 376 may be configured to transmit light through the distal end only in an upper portion of the inside of the upper clothing 300 (a portion adjacent to a location that corresponds to a location of the wearer's pulmonary artery).
The type of the first light source 370, the second light source 374, and the third light source 378 is not restricted. Examples of the first light source 370, the second light source 374, and the third light source 378 include LEDs and cold lamps. Light emitted by the first light source 370 enters from a surface of the proximal end of the first light guides 368, then the light is guided within the light guides 368, and the light exits from first light transmitting portions 382. Light emitted by the second light source 374 enters from a surface of the proximal end of the second light guides 372, then the light is guided within the light guides 372, and the light exits from second light transmitting portions 384. Light emitted by the third light source 378 enters from a surface of the proximal end of the third light guides 376, then the light is guided within the light guides 376, and the light exits from third light transmitting portions 386. There may be a single light source. In this case, the single light source is optically connected to a plurality of first light guides 368, a plurality of second light guides 372, and a plurality of third light guides 376.
The illuminance of light emitted by the first light source 370, the second light source 374, and the third light source 378 is not restricted as long as the light can dissociate carbon monoxide from CO-Hb. The blood is preferably exposed to light emitted by the first light source 370, the second light source 374, and the third light source 378 at an illuminance of 100,000 lux or more. Exposure to light at an illuminance of less than 100,000 lux may not result in dissociation of carbon monoxide from CO-Hb. In the case, the blood is exposed to light at an illuminance of about 500,000 lux.
The upper clothing 300 may be used in, for example, the following manner. The upper clothing 300 is put on a wearer in a manner similar to common clothing so that the first light transmitting portions 382, the second light transmitting portions 384, and the third light transmitting portions 386 are positioned in a predetermined location. The upper clothing 300 transmits light having a wavelength of 600 to 750 nm through the first light transmitting portions 382, the second light transmitting portions 384, and the third light transmitting portions 386. The light transmitting time is not restricted. The light transmitting time is adjusted depending on the symptoms of the patient and the concentration of carbon monoxide in the blood.
As illustrated in
Other examples of the device include trocars that include a light emitter at the distal end, although the trocars are not shown herein.
Although the upper clothing 300 that includes the light emitters 360 in the front body 320 and the back body 340 is described, the light emitters 360 may be disposed only in the front body 320, or the light emitters 360 may be disposed only in the back body 340.
The upper clothing 300 and 400 may be configured in a manner similar to a down jacket. In this case, the light transmitting portions come in intimate contact with the wearer, which allows efficient transmission of light.
As illustrated in the following experiments, we developed the catheter 100 and the upper clothing 300 that can effectively dissociate carbon monoxide from CO-Hb and that can be used to remove carbon monoxide from the body. The catheter 100 and/or the upper clothing 300 is expected to be used in combination with, for example, breathing in concentrated oxygen, hyperbaric oxygen therapy, and jet ventilation for treatment of carbon monoxide poisoning.
In an Experiment 1, the effect of light exposure on the binding of carbon monoxide to hemoglobin vesicles was examined.
Carbon monoxide-hemoglobin vesicles (CO-HbV) were prepared in the following manner. First, HbV was prepared by enclosing hemoglobin purified from outdated human packed red blood cells with a phospholipid bilayer membrane. In particular, HbV was prepared by passing liquid prepared by adding mixed-lipid-particles and hemoglobin to saline through a membrane filter having a predetermined pore size under pressure (extrusion method). The prepared HbV had a particle diameter of 262 to 269 nm, a Hb concentration of 10.0 to 10.6 g/mL, a lipid concentration of 6.9 to 7.2 g/mL, and an oxygen saturation of Hb of 23 to 35 Torr. Then, CO-HbV was prepared by bubbling carbon monoxide through the HbV at 15 mL/min for 60 minutes.
First, we examined whether carbon monoxide was dissociated from CO-HbV. Ten male Sprague Dawley (SD) rats that were 7 week old (with a body weight of from 255 to 282 g) were prepared. In the respective rats, 90% of the circulating blood was replaced with SALINHES (HES, 6% hydroxyethylated starch, Kyorin Pharmaceutical Co., Ltd.). And the subcutaneous tissue of the anterior chest of the respective rats was exposed. The 10 rats were randomly divided into a light exposure group of 5 rats and a light non-exposure group of 5 rats. Then, the CO-HbV obtained in the above manner was administered to the rats by intravenous injection at 25 ml/kg. After administration of the CO-HbV, the anterior chest of the rats in the light exposure group was exposed to light having a wavelength in the range of from 400 to 1000 nm using FLG-2 light source device (illuminance of 27,000 lux at a measurement length of 100 mm and 12,000 lux at 150 mm, and luminance of 21,500,000 cd/m2, Kyowa Optical Co., Ltd.). After 0 minute, 30 minutes, 60 minutes, and 90 minutes of the light exposure, arterial blood was collected from the respective rats. Then, the collected arterial blood was used to determine the saturation of the CO-HbV from the absorbance at the respective times.
Carbon monoxide-hemoglobin (CO-Hb) and oxyhemoglobin (O2-Hb) are known to have two absorption maximums. O2-Hb is reduced by addition of hydrosulfite to provide reduced hemoglobin (Hb) having a single absorption maximum. In contrast, CO-Hb is not reduced by addition of hydrosulfite. Thus, the sample after addition of hydrosulfite has a composite absorption-spectrum derived from CO-Hb and Hb. As CO-Hb in blood increases, the single absorption maximum shifts to a shorter wavelength, and the absorption maximums derived from CO-Hb shifts to a longer wavelength. Thus, carbon monoxide saturation can be determined from the relationship between absorbance ratio and CO-Hb.
The carbon monoxide saturation was calculated from absorbance, as a ratio of the amount of CO-Hb after a predetermined amount of time has elapsed to the amount of CO-Hb (100%) immediately after light exposure. The carbon monoxide saturation was measured in the following manner. 10 mL of 0.1% aqueous sodium carbonate was added to 50 μL of blood to be tested and was allowed to stand for 15 minutes to prepare a sample to be tested. Then, the absorption spectrum of the sample to be tested was measured at a wavelength of 500 to 600 nm. The sample to be tested had an absorption maximum of CO-Hb at 538 nm. Then, sodium hydrosulfite was added to the sample to be tested, and the absorption spectrum was measured again. The Hb had an absorption maximum at 555 nm. Then, the absorbance at 538 nm, which was an absorption maximum of the CO-Hb, and the absorbance at 555 nm, which was the absorption maximum of the Hb, of the sample to be tested were measured. Finally, E538/E555 was represented as A.
Oxygen was bubbled through the blood to be tested (for example, at 0.5 mL/min for 30 minutes) to prepare blood that contained oxygen at a saturated concentration and that was free of CO-Hb. The oxygen bubbling rate varies with the amount of the blood to be tested. Sodium hydrosulfite was added to diluted blood 1 that was prepared by adding 10 mL of 0.1% aqueous sodium carbonate to 50 μL of the blood and was allowed to stand for 15 minutes to prepare a reference sample 1. The absorbance at 538 nm, which is an absorption maximum of CO-Hb, and the absorbance at 555 nm, which is the absorption maximum of Hb, of the reference sample 1 were measured. Then, E538/E555 was represented as A0, which was 0.784.
Sodium hydrosulfite was added to diluted blood 2 that was prepared by adding 10 mL of 0.1% aqueous sodium carbonate to 50 μL of blood immediately after light exposure (after 0 minute of light exposure) and was allowed to stand for 15 minutes to prepare a reference sample 2. Absorbance at 538 nm, which is an absorption maximum of CO-Hb, and at 555 nm, which is the absorption maximum of Hb, of the reference sample 2 were measured. Then, E538/E555 was represented as A100, which was 1.17.
Then, the carbon monoxide saturation (%) was calculated by the following formula: (Ax−A0)/(A100−A0)×100.
As illustrated in
In Experiment 2, the effect of the intensity of irradiated light on the binding of carbon monoxide to human hemoglobin in human blood was examined.
First, blood was collected from adult male humans suffering from carbon monoxide poisoning. Part of the collected blood was exposed to light at an illuminance of 100,000 lux, 200,000 lux, and 500,000 lux. After 0 minute, 2 minutes, 4 minutes, 6 minutes, 8 minutes, 10 minutes, 12 minutes, 14 minutes, 16 minutes, 18 minutes, and 20 minutes of the exposure, part of the respective blood was collected and was examined for carbon monoxide saturation in the same manner as in Experiment 1. The human CO-Hb has absorption maximums of 538 nm and 568 nm, and the human O2-Hb has absorption maximums of 540 nm and 576 nm. The human Hb has an absorption maximum of 555 nm. A0 and A100 calculated from these values were 0.784 and 1.171, respectively.
As illustrated in
In Experiment 3, the effect of the wavelength of irradiated light on the binding of carbon monoxide to human hemoglobin in human blood was examined.
Blood was collected from adult male humans suffering from carbon monoxide poisoning in the same manner as in Experiment 1. Part of the collected blood is exposed to light at a wavelength of 680 nm using a light emitting diode. After 0 minute, 4 minutes, 8 minutes, 12 minutes, 16 minutes, and 20 minutes of the light exposure, part of the blood was collected, and the carbon monoxide saturation (%) was determined from the absorbance.
In Experiment 4, the effect of light exposure on the binding of carbon monoxide to human hemoglobin in porcine blood was examined in vitro.
Carbon monoxide was bubbled through porcine blood (by placing 50 mL of porcine blood into a bag filled with 4.5 L of pure carbon monoxide gas and stirring the mixture well) to prepare blood containing carbon monoxide at a saturated concentration. The carbon monoxide bubbling ratio varies with the amount of the porcine blood. Oxygen was bubbled through part of the prepared blood (at 40 mL/min) while exposing the blood to a light at an illuminance of 600,000 lux. Oxygen was bubbling through another part of the prepared blood (at 40 mL/min) without light exposure. After 0 minute, 5 minutes, 10 minutes, 15 minutes, and 20 minutes of the light exposure, part of the respective blood was collected, and the carbon monoxide saturation was examined in the same manner as in the Experiment 1. The results are shown in
As illustrated in
In Experiment 5, the effect of light exposure on the binding of carbon monoxide to human hemoglobin in dog blood was examined in vitro.
Carbon monoxide was added to dog blood (by placing 50 mL of dog blood into a bag filled with 4.5 L of pure carbon monoxide gas and stirring the mixture well) to prepare blood containing carbon monoxide at a saturated concentration. Oxygen was bubbled through part of the prepared blood (at 40 mL/min) while exposing the blood to light at an illuminance of 600,000 lux. Oxygen was bubbled through another part of the prepared blood (at 40 mL/min) without light exposure. After 0 minute, 5 minutes, 10 minutes, 15 minutes, and 20 minutes of the light exposure, part of the respective blood was collected, and the carbon monoxide saturation was examined in the same manner as in the Experiment 1. The results are shown in
As illustrated in
As described above, it was observed that light exposure resulted in dissociation of carbon monoxide from CO-Hb even in vitro experiments using human blood, dog blood, and porcine blood. Thus, we expected that exposure of CO-Hb in vivo to light at a predetermined wavelength also results in dissociation of carbon monoxide from CO-Hb. We also expected that use of a catheter and/or an upper clothing can lead to effective dissociation of carbon monoxide from CO-Hb. We also expected that combination of the catheter and/or the upper clothing with hyperbaric oxygen therapy or breathing in concentrated oxygen provides further improved therapeutic effect.
This application claims priority to JP 2013-235804, filed on Nov. 14, 2013. The entire contents of that application and the drawings therein are incorporated herein.
Our catheter and the upper clothing are useful as a catheter and an upper clothing as a device that treats carbon monoxide poisoning used to provide initial therapy for a patient suffering from acute carbon monoxide poisoning.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2013-235804 | Nov 2013 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2014/005744 | 11/14/2014 | WO | 00 |
