High Dose Inhalation with Gaseous Nitric Oxide in COVID-19 Treatment.

A method of treatment of a new coronavirus infection COVID-19 in patients undergoing high flow oxygenation is proposed and technically implemented; the method is based on high-dose inhalation of gaseous nitric oxide (NO) with the patient's spontaneous breathing. The results of the treatment of this disease demonstrating the high efficiency of the new method are presented. A possible mechanism of the blocking effect of high doses of inhaled nitric oxide on the replication of the SARS-CoV-2 virus is discussed; it is based on the formation of dinitrosyl iron complexes in the respiratory tract and lungs of COVID-19 patients with thiol-containing ligands acting as donors of NO and nitrosonium NO+ cations in a living organism that have a cytotoxic effect on the SARS CoV-2 virus.

Gaseous Nitric Oxide and Dinitrosyl Iron Complexes with Thiol-Containing Ligands as Potential Medicines that Can Relieve COVID-19.

It is shown that the inhalation of gaseous nitric oxide (gNO) or sprayed aqueous solutions of binuclear dinitrosyl iron complexes with glutathione or N-acetyl-L-cysteine by animals or humans provokes no perceptible hypotensive effects. Potentially, these procedures may be useful in COVID-19 treatment. The NO level in complexes with hemoglobin in blood decreases as the gNO concentration in the gas flow produced by the Plazon system increases from 100 to 2100 ppm, so that at 2000 ppm more than one-half of the gas can be incorporated into dinitrosyl complexes formed in tissues of the lungs and respiratory tract. Thus, the effect of gNO inhalation may be similar to that observed after administration of solutions of dinitrosyl iron complexes, namely, to the presence of dinitrosyl iron complexes with thiol-containing ligands in lung and airway tissues. With regard to the hypothesis posited earlier that these complexes can suppress coronavirus replication as donors of nitrosonium cations (Biophysics 65, 818, 2020), it is not inconceivable that administration of gNO or chemically synthesized dinitrosyl iron complexes with thiol-containing ligands may help treat COVID-19. In tests on the authors of this paper as volunteers, the tolerance concentration of gNO inhaled within 15 min was approximately 2000 ppm. In tests on rats that inhaled sprayed aqueous solutions of dinitrosyl iron complexes, their tolerance dose was approximately 0.4 mmol/kg body weight.

[An experimental substantiation of nitric-oxide containing gas flow in the treatment of eye traumas]. / Eksperimental'noe obosnovanie primeneniia oksida azota v gazota v gazovom potoke dlia lecheniia travm glaza.

The hypothesis on the biostimulating effect of exogenous nitric oxide (NO) was made use of to develop a new method to stimulate the healing of wounds through treating them by a NO saturated gas flow. The above gas flow is generated by air-plasma unit "Plazon". The experimental and clinical studies confirmed that the NO-therapy is a highly effective treatment method for different lesions of the skin and soft tissues. We tried to use the above method in ophthalmology. A comprehensive experimental study was carried out to assess the impact of the NO-containing gas flow on the eyeball structures. An optimal mode was designed, which does not exert any influence on the intraocular pressure, Ph of the lachrymal fluid, antioxidative activity and on the proteinase-inhibitor balance in tears; no morphological changes occurred in the ocular tissue structures. The mentioned morphological and biochemical studies confirmed that the application of the NO-containing gas flow speeds up the healing, process of both an experimental cornea erosion and penetrating corneal wounds. Optimal modes of NO-therapy were defined for both types of lesions.

[Effects of gaseous flow containing nitric oxide on the eyeball structures (an experimental study)]. / Vliianie gazovogo potoka, soderzhashchego oksid azota, na struktury glaznogo iabloka (éksperimental'noe issledovanie).

Nitric oxide is one of the main factors of intra- and intercellular regulation in the organism. Its vasodilating, antiaggregant, antithrombogenic, antibacterial, anticarcinogenic, and immunogenic effects are well known. It stimulates the reparative processes in soft tissue injuries. We failed to find reports about the role of NO in the wound process in the eyes. The source of NO in our experiments was medical air-plasma device Plason. Exposure of the eye to NO-containing gaseous flow did not cause changes in the lacrimal pH; NO penetrated through the cornea and sclera, exerted no appreciable cytotoxic effect on the surface epithelium of the eye, did not change the intraocular pressure, and caused no morphological changes in ocular tissues. On the other hand, NO-containing gaseous flow had an appreciable lasting effect on the diameter of the conjunctival vessels, this effect being dose-dependent. The doses of NO-containing gaseous flow which can be used in the treatment of eye wounds were determined.

[Local application of low-energy aerial and argon plasma in the treatment of suppurative wounds and trophic ulcers]. / Mestnoe primenenie nizkoénergeticheskoi vozdushnoi i argonovoi plazmy v lechenii gnoinykh ran i troficheskikh iazv.

The authors describe experimental and clinical (113 patients) data demonstrating the antimicrobial, hemostatic and stimulating the regenerating processes property of the low energy plasma in local treatment of purulent and long-standing wounds and trophic ulcers.

[Use of a new biological factor--exogenous nitric oxide--during surgical treatment of periodontitis]. / Primenenie novogo biologicheskogo faktora-ékzogennogo oksida azota-pri khirurgicheskom lecheni parodontita.

In order to improve the efficiency of surgical treatment of periodontitis, the operative wound was exposed to nitrogen oxide (NO) during osteogingivoplasty and on days 3, 5, and 6 after it. Clinical and laboratory data making use of the cytomorphometrical method indicate that NO exposure decreased and maybe prevented secondary injury to the operation wound in up to 46.6% patients, which was confirmed by decrease and even normalization of destruction index and inflammatory destructive index on days 7 and 14, which was not observed in the reference group patients not exposed to NO.

[The use of air-plasma flows in military field surgery and disaster medicine]. / Primenenie vozdushnykh plazmennykh potokov v voenno-polevoi khirurgii i meditsine katastrof.

Plasma currents of high energy are considered to be very promising in the surgical treatment of modern pathology. The scientists of this country have constructed a portable field surgery apparatus in which a heated atmospheric air assumes a form of a high-temperature thin jet used like a surgeon's scalpel. Experiments and clinical tests proved the efficacy of this microplasmotron that can destroy and coagulate body tissue when treating it with plasma. This new method has, besides hemostatic action, some noticeable antimicrobic effect that leads to acceleration of tissue granulation and wound healing. In specialized and skilled medicare this progressive and priority method should be applied for initial surgical wound treatment, secondary hemorrhage arrests and surgical interventions when a high risk of infection spreading is involved.

[Use of physical plasma in surgery of wounds and wound complications]. / Ispol'zovanie fizicheskoi plazmy v khirurgii ran i ranevykh oslozhnenii.

The article is devoted to the local application of high energy plasma flows in the complex treatment of wounds and wound complications. The new technology of physical action upon the biological tissues allows performing dissections, evaporation and carrying on local hemostasis and sterilization of the wound surface simultaneously. The shortening of the first phase of the wound healing process and earlier development of the second phase are due to the "biophysical isolation" of the wound surface by the thermal necrosis layer from unfavorable effects of the external medium. The healing goes on by the type of productive inflammation. The use of plasma flows during surgical treatment of purulent wounds reduces pains during the postoperative period and considerably improves results of the treatment.

[Possibilities of using plasma flow in lung surgery]. / Perspektivy primeneniia plazmennogo potoka v legochnoi khirurgii.

Experiments on 10 mongrel dogs demonstrated the efficacy and reliability of argon plasma flux in achieving hemo- and aerostasis in surgical debridement of gunshot wounds of the chest "Fakel" plasma surgical complexes were used as a source of plasma. A total of 43 operations were performed on patients whose ages ranged from 16 to 68 years: pulmonectomy 3, lobectomy 24, bilobectomy 4, atypical resection of the lung 4, pleurectomy with lung decortication 5, diagnostic thoracotomy 2, rib resection 1. Argon plasma flux was used in thoracotomy, treatment of wound surfaces of the lungs and pleura, separation of the interlobar fissures, and division of the main and lobar bronchi. The plasma flux produced an analgesic effect; as a result much less narcotics and analgesics were needed and physical activity was permitted earlier. The amount of discharge from the pleural cavity along the drain was 1.5-2 times less (200 +/- 40 ml) as compared to that in the traditional methods for conducting similar operations. No complications associated with application of plasma flux were noted. Incompetence of the bronchial stump, rethoracotomy for bleeding or suppuration were not encountered.

[The Fakel-7 plasma surgical unit in operations on the bladder (experimental research)]. / Plazmennyi khirurgicheskii kompleks "Fakel-7" pri operatsiiakh na mochevom puzyre (èksperimental'noe issledovanie).

The study was undertaken to examine the effect of plasma flow on the urinary bladder of 15 mongrel dogs in acute and chronic experiments. The acute experiment defined the power of plasma flow in operations on the bladder. Morphological studies comparatively assessed the bladder wall damaged with a CO2 laser. The chronic experiment examined morphological changes in a bladder wound 1-30 days following exposure to plasma flow. The processes of healing of the urinary bladder wound were found to end in formation of a thin connective tissue scar on day 20, as with laser radiation, and be followed by a far less inflammatory reaction within the first 7 days. The application of a Fakel-7 plasma surgical complex as a destructor was admitted to be promising in operatively removing the abnormally changed tissues of the bladder wall in the clinical setting.

[Experimental and clinical studies and prospects of using plasma flows]. / Eksperimenta'lnoe i klinicheskoe izuchenie i perspektivy primeneniia plazmennykh potokov.

The article deals with experimental studies in the choice of a plasma-forming gas and optimization of the operating regimen of a plasma surgical device to be used in surgical practice. On the basis of these studies, methods of operations on the liver were developed. Clinical experience in practical removal of a malignant tumor of the anterior abdominal wall with the use of a plasma device is discussed. The developed methods of hemostasis by means of a plasma flow of argon may be used in urology, thoracic surgery, gynecology, and military surgery.