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LASER PHYSICS AND ENGINEERING Optical method and apparatus for detoxicating the poisonous action of carbon monoxide M. M. Asimov,a) V. Yu. Plavskiı˘, A. B. Krasnobaev, D. B. Vladimirov, and A. N. Rubinov B. I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk, Belarus

R. M. Asimov OOO Sensotronika, Belarusian High Technology Park, Minsk, Belarus

(Submitted November 20, 2012) Opticheskiı˘ Zhurnal 80, 3–8 (August 2013) This paper proposes and discusses a fundamentally new approach to eliminating the poisonous action of carbon monoxide. A technology based on the phenomenon of laser-induced photodissociation of carboxyhemoglobin in the blood vessels and capillaries has been developed. The spectra of the action of carboxyhemoglobin and oxyhemoglobin in the cutaneous blood vessels are calculated by numerically modeling the interaction of laser radiation with biological tissue. Criteria are determined for the efficiency of the induced photodissociation of carboxyhemoglobin when the radiation acts directly on the pulmonary alveoli, through the epidermis, and intravenously. © 2013 Optical Society of America. OCIS codes: (350.4600) Optical engineering; (300.6360) Spectroscopy, laser. http://dx.doi.org/10.1364/JOT.80.000470

The problem of efficiently eliminating the poisonous action of carbon monoxide is a crucial and socially significant task. The possibilities of modern medicine have remained extremely limited, and therefore casualties that result from poisoning remain significant.1–4 Carbon monoxide is a powerful toxic gas with no color or smell. The toxicity of carbon monoxide for the human organism is associated with the formation of a strong complex when it combines with blood hemoglobin (Hb) to form carboxyhemoglobin (HbCO). The HbCO complex is hundreds of times more stable than that of the complex of Hb with oxygen (O2 )—oxyhemoglobin (HbO2 ).5 An increase of the concentration of HbCO in the blood reduces the transport of O2 by hemoglobin to the vitally important organs and tissues. The process by which CO binds to Hb while O2 is liberated from the HbO2 complex occurs as simultaneous and mutually conjugate reactions: HbO2 CO HbCO O2 ↑. The formation of the HbCO complex blocks the oxygenation of Hb and breaks down its oxygen-transport function. This causes hypoxia—a deficit of oxygen in the blood plasma and biological tissues. The problem of efficiently eliminating the poisonous action of carbon monoxide requires new approaches in the development of modern high-efficiency methods. 470

J. Opt. Technol. 80 (8), August 2013

An optical method of eliminating the poisonous action of carbon monoxide, based on the laser-induced photodissociation of the HbCO complex of blood,6 has been proposed and studied experimentally in vivo at the Institute of Physics of the National Academy of Sciences of Belarus. A method of extracorporeal irradiation of blood is presented in this paper, and an apparatus has been developed for using it in clinical practice. The proposed method and device for extracorporeal irradiation of blood make it possible to increase the efficiency with which an organism is detoxicated from the poisonous action of carbon monoxide by an order of magnitude in comparison with the method of forced ventilation of the lungs with oxygen or hyperbaric oxygenation (HBO) of the organism.6 The laser-optic system is equipped with two modules, which are intended for the detoxication of the organism as a function of the degree of seriousness of the poisoning with carbon monoxide. The criterion for the efficiency of using the corresponding module is the degree of seriousness of the poisoning with carbon monoxide, determined by the concentration of the HbCO complex in the blood. In medical practice, light and medium degrees of seriousness of poisoning are assigned to cases in which CO binds from 10% to 30% of the blood Hb; a serious degree of poisoning corresponds to the case in which carbon monoxide bonds from 30% to 60% of the blood Hb, and this presents danger to human life. In clinical practice, one method of eliminating the poisonous action of carbon monoxide is to hyperventilate the lungs with 100% oxygen through an oxygen mask or under

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EXPERIMENTAL STUDY OF THE PHOTODISSOCIATION OF CARBOXYHEMOGLOBIN IN VITRO

The photodissociation efficiency of carboxyhemoglobin HbCO in vitro as a function of the action of laser radiation 471


with various wavelengths has been experimentally studied, using the results of numerical modeling. Figure 1 shows the Q spectra—the absorption bands of blood HbO2 , HbCO, and Hb—normalized to unity. As can be seen, the shapes of the absorption bands of HbO2 and HbCO in this spectral range are very similar and have two pronounced maxima, at λ 545 and 580 nm and λ 540 and 570 nm, respectively. These spectra are characterized by the fact that the absorption band of HbCO is virtually cut off at 640 nm. This circumstance was taken into account when developing an optical method for the photodetoxication of the poisonous effect of carbon monoxide. Venous blood stabilized with an anticoagulant (heparin, EDTA) was used in the in vitro experiments. The optical density at the chosen wavelengths was measured with an SF-16 spectrophotometer. The carboxyhemoglobin concentration was calculated from %HbCO D531 X − D538 X∕D531 HbCO − D538 HbCO: After the optical density DX of the sample was determined, it was saturated with 100% carbon monoxide in order to transform the entire hemoglobin content into carboxyhemoglobin, and the optical density was again measured as DHbCO. The DX∕DHbCO ratio determines the percentage of carboxyhemoglobin in the blood. Carbon monoxide was obtained by the reaction between concentrated sulfuric and formic acids boiled in a flask with a closed cover and a gas-outlet tube.11 The concentrated sulfuric and formic acids were mixed in a 1∶1 ratio. HCOOH→t; H2 SO4 H2 O CO↑. To determine the carboxyhemoglobin, CO gas was passed through a prepared solution of blood for 10 min. The starting concentration of carboxyhemoglobin in blood was 2% on the average, with an error of ≈3%. 1.0 0.9 0.8

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conditions of artificial ventilation of the lungs through an intubation tube. HBO of biological tissues is currently considered to be the most efficient method. At the same time, the advisability of using HBO to treat carbon monoxide poisoning has not been completely clarified.7 The prolonged action of carbon monoxide at concentrations several times the maximum permissible exposure damages the cardiac muscle and breaks down the coronary blood circulation. This kind of change is accompanied by an increase of the concentration of hemoglobin in the blood. A high concentration of HbCO in the blood is typical of acute intoxication, whereas, with chronic poisoning, it insignificantly (10% or more) exceeds the norm of 5%. The treatment of serious forms of acute carbon monoxide poisoning is based on oxygen therapy. The most effective way to treat medium-level, or especially high-level acute carbon monoxide poisoning remains the method of HBO of the biological tissue.8 When the HBO method is used, the mean oxygen pressure in the chamber must be 1–1.5 atm, or in serious cases up to 2–2.5 atm. The overall duration of the session is 80–90 min. Usually one HBO session is carried out in the course of a day. In the most serious cases, the HBO sessions can be repeated up to four times per day. At the same time, the HBO method has limitations to extensive use, especially a side effect associated with oxygen intoxication when it is applied for a long time.6,7 Moreover, it is tedious and complex in technical operation. The rate of splitting of CO and Hb is extremely low: at an HbCO concentration in the blood of about 20%, its half-decay period is at least eight hours.8 The method of forced ventilation of the lungs with pure oxygen makes it possible to reduce this time, but, when the concentration of HbCO in the blood is greater than 60%, carbon monoxide is the main cause of hypoxia in people killed in fires. The search for ways to effectively eliminate the poisonous action of carbon monoxide is consequently a crucial task. Because the possibilities of modern medicine are extremely limited, losses from carbon monoxide poisonings remain significant. Even though the binding of CO in a complex with Hb is significantly stronger than in a complex of O2 with Hb, the photodissociation efficiency of HbCO is almost an order of magnitude greater (98%) than that of HbO2 (10%) in the visible spectrum.9,10 The large difference in the photodissociation quantum yields makes it possible to break down the HbCO complex in blood with high selectivity. Whereas the efficiency of previously known methods remains extremely low, the forced breakdown of HbCO by photodissociation while simultaneously saturating the blood plasma with molecular oxygen makes it possible to speed up the discharge of CO from the organism. This paper presents experimental results and a device for extracorporeal irradiation of blood with LED sources for detoxication of the poisonous action of carbon monoxide.

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λ, nm FIG. 1. Spectra of the Q absorption band of oxyhemoglobin (HbO2 )—(1), carboxyhemoglobin (HbCO)—(2), and hemoglobin (Hb) of blood—(3). Asimov et al.

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The blood was saturated with 100% CO for 10 min and was then treated with optical radiation at a wavelength of 514.5 and a power of 5.5 mW. To eliminate the carbon monoxide given off as a result of the photodissociation of carboxyhemoglobin and to prevent it from being recoupled to the hemoglobin, the blood was saturated with oxygen in parallel with the laser irradiation. The results of this experiment show that the effect of 10 min of laser radiation is to reduce the carboxyhemoglobin concentration by 15% by comparison with the initial concentration, i.e., 100% saturated with CO. It is interesting to point out that no decrease of the carboxyhemoglobin is observed when radiation at a wavelength of 632.8 nm acts under similar conditions. This experimental result is in complete agreement with the data of the numerical modeling and the calculation of the action spectrum, which predicted that the action of red light does not produce photolysis of HbCO. We also point out that, in the absence of irradiation, blood with 100% saturation with CO does not exhibit any changes of the HbCO concentration during a time equal to the time that the optical radiation acts, and this shows that the bond of CO with hemoglobin is strong. The results of numerical calculations12 and the experimental data thus make it possible to determine which wavelengths of optical radiation can efficiently break down carboxyhemoglobin by acting on the blood vessels in vivo through the epidermis, directly on the alveoli in the lungs, or intravenously. As pointed out above, the mechanism and physical principle of the photolysis of carboxyhemoglobin remains unchanged in all the cases considered here. It essentially consists of the following photophysical process: hv

HbCO4 →Hb CO4 4O2

poisonous action of carbon monoxide. We should point out that the patents listed in Refs. [13,14] were used in developing a device based on a method of deactivating carboxyhemoglobin in blood and a method of increasing the local concentration of oxygen in biological tissue. DEVICE FOR THE EXTRACOPOREAL PHOTOLYSIS OF THE CARBOXYHEMOGLOBIN OF BLOOD

As a result of studies carried out both with numerical modeling of the interaction of laser radiation with the HbCO of blood and experimental measurements in vivo, a device has been developed for phototherapy of the poisonous action of carbon monoxide. The apparatus is based on the extracorporeal irradiation of blood with optical radiation in the wavelength range 530–560 nm. The LED sources were chosen in emission wavelength and output power to match the absorption-band maxima of the HbCO of blood (Fig. 1). An external view of the apparatus for the extracorporeal irradiation of blood to detoxicate the poisonous action of carbon monoxide is shown in Fig. 2. This apparatus is a compact device with three main modules: a spiral cell with the sample of blood for irradiation, a peristaltic pump to produce circulation of the blood, and an optical system that irradiates the blood with LED sources on two sides. The light sources are chosen to match the absorption-band maxima of the HbCO in the visible region. The device has the following main technical characteristics:

• the time to establish the working regime of the apparatus

after switching on is at most 5 min; • the blood-pumping rate is 5, 10, and 15 mL∕ min; • the error of the blood-pumping rate is no greater than 20%; • the spectral range of the radiation extends from 530 to 630 nm; • the continuous operating time of the apparatus is at least 8 h;

↓ HbO2 4 The choice of one way of photodeactivation or the other in clinical practice should be based on the degree of carbon monoxide poisoning. Three degrees of seriousness of carbon monoxide poisoning are considered in classical practice. In weak poisoning, the HbCO concentration in the blood does not exceed 10%. In this case, it is best to carry out photodissociation in a noninvasive way, through the epidermis. In medium-level poisoning, when the HbCO concentration does not exceed 30%, it is more efficient to irradiate the blood directly in the alveoli of the person’s lungs. With HbCO concentrations greater than 30%, the most effective means of deactivation is by intravenous or extracoporeal irradiation of the blood. This method is invasive but is well developed in clinical practice in hemolysis, or the UV irradiation of blood. Below we give the characteristics of a device for the extracorporeal irradiation of blood by LED sources, with the photodetoxication of blood from the 472


FIG. 2. External view of apparatus for the extracorporeal irradiation of blood with LEDs. Asimov et al.

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CONCLUSIONS

An optical method has been proposed and considered for eliminating the poisonous action of carbon monoxide. The method thus developed is based on the phenomenon of laser-induced photodissociation of carboxyhemoglobin in the blood vessels and capillaries. Criteria have been established for the efficiency of laser-induced photodissociation of carboxyhemoglobin in blood directly irradiated in the pulmonary alveoli, through the epidermis, and intravenously. It has been shown that, when radiation with a wavelength of 514.5 nm acts on carboxyhemoglobin, a reduction of its concentration by 15% in 10 min is observed. This provided a scientific basis for developing a high-efficiency optical method for eliminating the poisonous action of carbon monoxide. a)

Email: [email protected]‐net.by

FIG. 3. Cell for irradiating blood with LED radiation sources.

• information

on the operating regimes of the apparatus is shown on an alphanumeric display; • the supply voltage is 230 22 V with a frequency of 50 Hz; • the required power is no greater than 80 VA; • the overall dimensions are no greater than 260 × 250× 143 mm; • the mass of the apparatus is at most 7 kg. The apparatus is equipped with a system that prevents the cell from being removed during operation. Figure 3 shows the cell for irradiating the blood with LEDs. The blood circulates in a medical tube wound in the form of a spiral so as to maximize the irradiation of the cell, with LEDs along both sides. Planar LEDs of various spectral ranges and output powers of the optical radiation are used in the apparatus. The algorithm for operating the apparatus involves selective switching on and off of the individual LEDs, and this makes it possible to vary the parameters of the luminous action (the wavelength of the incident light or the combination of wavelengths, optical power of the radiation, etc.) to achieve the necessary therapeutic effect. The irradiation dose can be increased or decreased by varying the rate at which the blood is pumped. All the models of LEDs that are used undergo certification to meet the requirements of the European Union “Reduction of Hazardous Substances.” The Nichia LEDs also underwent certification by the International Electric Commission (IEC). The apparatus for extracorporeal irradiation of the blood can be widely applied in modern medicine and can be used for the Ministry of Emergency Situations to clean up the consequences of fires and technogenic catastrophes.

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1T. Meredith and A. Vale, “Carbon monoxide poisoning,” Braz. J. Med. Biol. Res. 296, 77 (1988). 2J. E. Peterson and R. D. Stewart, “Absorption and elimination of carbon monoxide by inactive young men,” Arch. Environ. Health 21, 165 (1970). 3W. J. Egan, W. E. Brewer, and S. L. Morgan, “Measurements of carboxyhemoglobin in forensic blood samples using UV–visible spectrometry and improved principal component regression,” Appl. Spectrosc. 53, 218 (1999). 4M. Goulon, A. Barois, M. Rapin, F. Nouailat, S. Grosbuis, and J. Labrousse, “Carbon monoxide poisoning and acute anoxia,” J. Hyperbaric Med. 1, 23 (1986). 5P. Croker, “Carbon monoxide poisoning: the clinical entity and its treatment. A review,” Mil. Med. 149, 257 (1984). 6P. S. Grim, L. J. Gottlieb, A. Boddie, and E. Batson, “Hyperbaric oxygen therapy,” J. Am. Med. Assoc. 263, 2216 (1990). 7C. Piantadosi, “The role of hyperbaric oxygen in carbon monoxide, cyanide and sulfide intoxications,” Probl. Respir. Care 4, 215 (1991). 8P. M. Tibbles and J. S. Edelsberg, “Hyperbaric-oxygen therapy,” N. Engl. J. Med. 334, 1642 (1996). 9B. M. Dzhagarov, V. S. Chirvonyı˘, and G. P. Gurinovich, Laser Picosecond Spectroscopy and Photochemistry of Biomolecules, V. S. Letokhova, ed., (Nauka, Moscow, 1987), pp. 203–212. 10W. A. Saffran and Q. H. Gibson, “Photodissociation of ligands from hem and hem proteins: effect of temperature and organic phosphate,” J. Biol. Chem. 252, 7955 (1977). 11V. F. Kramerenko, Yu. A. Sobchuk, and T. N. Gladyshevskaya, Methodological Indications of the Quantitative Determination of Carboxyhemoglobin and Carboxymyoglobin (Moscow, 1974). 12M. M. Asimov, R. M. Asimov, and A. N. Rubinov, “Laser-induced photodissociation of carboxyhemoglobin: an optical method for eliminating the toxic effect of carbon monoxide,” Opt. Spektrosk. 109, 1320 (2010) [Opt. Spectrosc. 109, 237 (2010)]. 13M. M. Asimov, R. M. Asimov, and A. N. Rubinov, “Method of deactivating the carboxyhemoglobin of blood,” Russian Patent No. 2,408,400 (2011). 14M. M. Asimov, R. M. Asimov, and A. N. Rubinov, “Method of increasing the local concentration of oxygen in biological tissue,” Eurasian Patent No. 015215 (2011).

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