Method for emergency relief of acute ischemic attacks

Abstract

The invention relates to the field of medicine, and more particularly to emergency medical assistance. A respiratory intervention is performed on a patient with an artificial gas-air mixture having an increased content of argon of at least 30 vol %, enabling this artificial gas-air mixture to be effective continuously throughout the procedure. Furthermore, the respiratory gaseous medium has an increased content of oxygen with xenon being added and has the following composition: 1-10 vol % of xenon; 30-35 vol % of argon; 60-65 vol % of oxygen. The intervention on the patient with the artificial gas-air mixture of the composition mentioned is performed for 20-40 minutes or more, until specialized medical assistance is given. The method makes it possible to increase the effectiveness, safety and rapidity of relieving acute cerebral and cardiac ischemia, and to reduce the risk of developing an acute cerebral stroke or myocardial infarction.

Claims

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6. A medicinal composition for emergency management of acute ischemic attacks with impaired cerebral or coronary circulation, the composition comprising an artificial gas mixture of up to 60-65 vol. % of oxygen, up to 30-35 vol. % of argon, up to 1-10 vol. % of xenon, and nitrogen.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

ADVANTAGEOUS EFFECTS OF INVENTION

[0040] As found in numerous studies conducted by the authors, the clinical effect of the use of artificial respiratory media with increased argon content, altered (increased) oxygen content, as well as xenon included in their composition, is provided by an increase in the volume of oxygen delivered to tissues and organs damaged by an acute ischemic attack with impaired cerebral or coronary circulation, acceleration of its mobilization, as well as an increase in the coefficient of efficiency of oxidative processes, allowing to reach the necessary level of energy supply of damaged or functionally depleted cells. In this case, the additional supply of tissues with oxygen is carried out in the absence of toxic effects of excess oxygen content, as it takes place when breathing with pure oxygen or oxygenobarotherapy.

[0041] The study of biological effects of argon has begun relatively recently and led to the discovery of facts indicating organoprotective and neuroprotective effects when exposed to oxygen-argon breathing mixtures. According to the authors of the monograph “Basics of barophysiology, diving medicine, barotherapy and inert gas treatment” (B. N. Pavlov et al edited by A. I. Grigoryev, M., Publ. Granp Poligraf, 2008, p. 378-380), the basis of these and other favorable effects of argon is its pronounced antihypoxic effect associated with facilitation of oxygen transfer to cells from the blood, as well as improved oxygen utilization, resulting in “pushing back” the threshold of terminal hypoxia and cell death, expanding the functional potential of cells, tissues and the body as a whole.

[0042] Positive effect of argon on metabolic processes in cells and tissues is confirmed by comparative studies on preservation of organs for transplantation (in particular, kidneys) in Celsior+argon, Celsior+xenon, Celsior+atmospheric air solution and subsequent heterotopic transplantation. Kidney transplantation stored in Celsior+argon medium has been shown to increase survival (7/8 vs. 3/8 pigs survived after surgery) and faster recovery of renal function (creatinine clearance, duration of tubulopathy, proportion of sodium excreted were evaluated) (see Faure A., Bruzzese L., Steinberg J. G., Jammes Y., Torrents J., Berdah S. V., Gamier E., Legris T., Loundou A., Chalopin M., Magalon G., Guieu R., Fenouillet E., Lechevallier E. Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation//J. Transl. Med. 2016, V. 14).

[0043] The neuroprotective effect of gas breathing media containing argon has also been described in a number of works. The studies confirm the positive effect of argon on the tolerance of hypoxic conditions; a positive effect of ischemic postconditioning with gas mixtures of 70 vol. % Ar, 30 vol. % 02 for one hour had been shown, which resulted in a decrease in cortical neuronal death and severity of neurological symptoms compared with classical resuscitation (see, for example, Brucken A., Kurnaz P., Bleilevens C., Derwall M., Weis J., Nolte K., Rossaint R., Fries M. Dose dependent neuroprotection of the noble gas after cardiac arrest in rats is not mediated by K(ATP)-channel opening//Resuscitation, 2014. V. 85, No. 6-pp. 826-832). At the same time, in experiments on rats and pigs, the neuroprotective properties of argon proved to be dose-dependent. At the same time, after artificially induced ischemia in the experimental subjects, the application of the above argon-containing ARGM produced a positive neurological effect.

[0044] Therefore, the use of oxygen-argon mixtures (in an approximate ratio of 65:35 or close to it) for elimination of extreme and terminal hypoxic states (in normobaric and hyperbaric variants) is the method of choice in nonpharmacological care for patients in such states. Cerebral or coronary circulatory disorders belong to such conditions.

[0045] Prospects for the use of another inert gas—xenon—to relieve acute ischemic attacks with impaired cerebral or coronary circulation and keep patients alive are due to its unique physical and chemical properties. Xenon combines low toxicity with the ability to dissolve in biological fluids and cell membranes and affect metabolic and cellular processes. First of all, xenon is used as an anesthetic and pain reliever (a mixture of oxygen and xenon), with properties approaching those of an “ideal anesthetic” (see Burov N. E. Xenon in anesthesiology.—M.: Puls, 2000. 291 p.). It helps to quickly put a patient to sleep; once anesthesia ceases, there is a quick and easy awakening without any undesirable effects, such as irritation of the respiratory tract, respiratory depression, toxic effects, etc. Medical xenon is not addictive and is eliminated from the body within minutes. Meanwhile, the achieved effect lasts for a longer time. In anesthesia practice, xenon-oxygen mixtures are used in approximate ratios of 50:50 and close to them.

[0046] At the same time, such mixtures with a lower content of xenon (10-20 vol. %) can be used in rehabilitation, sports and occupational medicine for urgent reduction of physical fatigue, relief of psycho-emotional stress, normalization of sleep, and correction of borderline functional states (see, for example, Kalmanov A. S. et al. Operational correction of functional condition of divers by inhalation of special xenon gas mixtures during training sessions II Aerospace and environmental medicine. 2016. T. 50. No. 3. P. 48-54). In this case, xenon acts as a means of artificial decrease in the activity of neurons of the higher sections of the cerebral cortex and other parts of the brain, which can be considered as a kind of “parabiotic” effect.

[0047] It is known that the parabiosis state is characterized by a significant reduction of energy and oxygen demand of the most active cells and tissues, as well as their transition to the most economical level of functioning while maintaining vitality and possibility of recovery. Therefore, the inclusion of xenon at low concentrations into the said oxygen-argon mixture for the purpose of relieving acute ischemic attacks with impaired cerebral or coronary circulation is pathogenetically sound, as in this case, the antihypoxic effects of oxygen and argon will be synergistically combined with xenon-induced significant reduction of oxygen and energy demand of vital tissues and organs and, first of all, the higher sections of CNS.

[0048] Experimental confirmation of these effects of inert gases were studies where the fact of significant prolongation of life of laboratory animals (in particular, rats) in a confined (without gas exchange) space when filling the chamber with oxygen-argon and oxygen-xenon mixtures compared with the presence of control group animals in an air environment (the initial oxygen concentration in all cases was the same) was proved. It was shown that when rats were exposed to argon medium, oxygen consumption was reduced by an average of 27% compared to the control, and the maximum survival time increased by 33%. Oxygen consumption in xenon decreased by 3.2 times, the time of maximum animal survival increased by 3.5 times (see Ananyev V. N. Effect of inert gases on oxygen uptake in an enclosed space in normobaric conditions II Materials of the IX All-Army Scientific-Practical Conference with International Participation “Barotherapy in complex treatment and rehabilitation of the wounded, sick and affected persons.”—Saint-Petersburg., 2015. P. 80.).

[0049] In addition, proof of the effectiveness of using inhaled gas mixtures was obtained in experimental studies in the application of oxygen-argon-xenon mixtures to keep alive laboratory animals with acute massive blood loss of severe degree. It was found that placing rats with massive blood loss in a chamber with oxygen-argon-xenon gas environment for a period of 8 hours significantly improved animal survival: 3 out of 24 animals of the experimental groups died (mortality 12.5%). In the control group of rats with similar blood loss in a gas medium with similar nitrogen oxygen content, 5 out of 12 individuals died within 8 hours (lethality 41.7%, p<0.05).

[0050] Thus, considering the specifics of action of each of the gases described on the body, their safety and ease of use, the authors proposed an inhalation gas mixture containing xenon—1-10 vol. %; argon—30-35 vol. %, oxygen—60-65 vol. % for use as a means of relieving acute ischemic attacks in premedical care and self-help. The time of application of this mixture is governed by the general therapy regimen and should be at least 20 to 40 minutes, which is enough time for the arrival of the ambulance.

Description of Embodiments

[0051] The stated concentrations of gases in the artificial gas mixture (ARGM) are justified by the following arguments. Progressive growth of tissue oxygen supply due to increased oxygen diffusion from alveoli into blood takes place at normal pressure when the oxygen content in the inhaled air increases to about 60-65 vol. %. At higher concentrations of oxygen in ARGM, the rate at which it enters the body slows down due to the extremely low solubility of this gas in blood and complete oxygen saturation of circulating hemoglobin of arterial blood. In addition, when breathing pure oxygen or ARGM with more than 65 vol. %, the risk of so-called oxidative stress increases—it is a cascade of biochemical hyperperoxidation reactions, the products of which have a pronounced toxic effect on body cells, which can aggravate the damaging effects of the ischemic attack. The content of xenon inert gas in ARGM, exceeding 10-15 vol. %, can also lead to intoxication of damaged cells and, above all, of neurons of the higher brain cortex, which is especially dangerous in cerebral stroke or the risk of its development. Moreover, the introduction of a patient into xenon anesthesia at the stage of premedical care is inadmissible. As for the optimal concentration of argon in ARGM, numerous studies have proved that the optimal antihypoxic and organoprotective effect of this gas is achieved at its content in a normobaric breathing mixture in the range of 30-35 vol. %. The higher content of argon, on the one hand, is ineffective, and on the other hand, it can also be accompanied by the risk of developing toxic effects on ischemic tissues.

[0052] The claimed method of relieving acute ischemic attacks with impaired cerebral or coronary circulation by using argon-containing respiratory gas mixtures with an increased oxygen and xenon content is carried out as follows. A patient with primary signs and suspected stroke or heart attack is transferred to artificial gas breathing with an individual inhalation device (a mask or mouthpiece), containing xenon 1-10 vol. %, argon 30-35 vol. %, and oxygen 60-65 vol. %.

[0053] In this case, the impact on a patient with an acute ischemic attack artificial gas mixture of the specified composition is carried out mainly at the stage of premedical care before delivery to the hospital, for 20-40 minutes or more. At the same time, if necessary, exposure of the patient to ARGM of the specified composition can also be carried out during the provision of specialized medical care, for example, when transporting the patient to a hospital.

[0054] In addition, if necessary, the artificial gas mixture of the above composition can be used under hospital conditions during resuscitation of patients with an acute ischemic attack and impaired cerebral or coronary circulation.

[0055] A face mask, respirator or mouthpiece, connected to a cylinder with oxygen-argon-xenon gas mixture of the specified composition can be used as an individual inhalation device.

INDUSTRIAL APPLICABILITY

[0056] The physiological effects arising as a result of and in the period of exposure to these gases on the body allow “postponing” the threshold of irreversible damage to the cells and tissues of vital organs, prolonging the patient's vitality, enabling his/her transportation to a medical facility to obtain qualified care.

[0057] The effect of this invention is to significantly reduce the probability and volume of brain and myocardial damage, as well as the lethal outcome at the stage of acute ischemic attacks with impaired cerebral or coronary circulation at the premedical stage in domestic conditions.