Nitric oxide therapy is beneficial to rehabilitation in professional soccer players: clinical and experimental studies.

Nitric oxide can activate neutrophils and macrophages, facilitate the synthesis of collagen, which allows significantly accelerating the regeneration of traumatized tissues. We studied the effects of nitric oxide-containing gas flow generated by plasma-chemical device "Plason" in a rat model of full-thickness wounds. Histological and morphometric analyses revealed that Plason treated wounds expressed significantly fewer signs of inflammation and contained a more mature granulation tissue on day 4 after the operation. Considering the results of the experimental study, we applied the Plason device in sports medicine for the treatment of lower limb bruises of 34 professional soccer players. Athletes were asked to assess the intensity of pain with the Visual Analogue Scale. Girths of their lower limbs were measured over the course of rehabilitation. Nitric oxide therapy of full-thickness wounds inhibited inflammation and accelerated the regeneration of skin and muscle tissues. Compared with the control, we observed a significant reduction in pain syndrome on days 2-7 after injuries, edema, and hematoma, and shortened treatment duration. This pilot study indicates that the use of nitric oxide is a promising treatment method for sports injuries.

Physicochemical parameters of NO-containing gas flow affect wound healing therapy. An experimental study.

Therapy of wounds and inflammatory diseases with NO-containing gas flows (NO-CGF) has proved to be effective in a longterm clinical practice. Plasma-chemical generation of nitric oxide occurs from atmospheric air in Plason device. For the purpose of modification and improvement of NO-therapy, effects of various physicochemical parameters of the NO-CGF on inflammatory and reparative processes in wounds were studied. Treatment of planar full-thickness skin wounds in laboratory rats was analyzed with morphological, immunohistochemical, morphometric and statistical methods. The study showed that the Plason device and the experimental device, which differs from Plason by the NO-CGF temperature, significantly reduce inflammatory and enhance regenerative processes in the wounds. The NO-CGF with an ambient temperature generated by the experimental device has noticeably facilitated the wound healing in direct ration to a nitric oxide content and flow velocity at the area of application. Temperature did not affect the course of wound healing process. The development of a new device for NO-therapy may be of use for both physicians and patients.

Study of plasma-chemical NO-containing gas flow for treatment of wounds and inflammatory processes.

This work is aimed at exhaustive and detailed study of chemical, physical and physico-chemical characteristics of NO-containing gas flow (NO-CGF) generated by a plasma-chemical generator of Plason device, which has been used in medical practice for more than 15 years for effectively healing wound and inflammatory conditions with exogenous nitric oxide (NO-therapy). Data was obtained on spatial structure of the gas flow, and values of its local parameters in axial and radial directions, such as nitric oxide content, velocity, temperature and mass flow density of nitric oxide, providing altogether the effectiveness of treatment by the exogenous NO-therapy method, were determined experimentally and by computations. It was demonstrated that plasma-chemical synthesis of NO from atmospheric air in a low direct current (DC) arc provides a high mass flow of nitric oxide at the level of 1.6-1.8 mg/s, while in the area of impact of NO-CGF on the biological tissue, on its axis, NO content is 400-600 ppm, flow velocity about 5 m/s, nitric oxide mass flow density 0.25-0.40 mg/(s·cm2), temperature 40-60 °C. Tendencies were determined for designing new devices for further experimental biological and medical research in the field of NO-therapy: lowering the temperature of NO-CGF to ambient temperature will enable variation, in experiments, of the affecting flow parameters in a wide range up to their maximum values: NO content up to 2000 ppm, velocity up to 20 m/s, nitric oxide mass flow density up to 2.5 mg/(s·cm2).

Beneficial effect of gaseous nitric oxide on the healing of skin wounds.

Intermittent daily exposures (60 s) to NO-containing gas flow (NO dose of 500 ppm) generated by air-plasma unit "Plason" improves healing of skin wounds in rats. The gas flow treatment shortened the recovery time of both aseptic and purulent wounds (300 mm2 area) by nearly a third. The treatment allows to achieve a marked improvement in the histological, histochemical, and electron-microscopic characteristics of the affected tissue. The mechanism of this phenomenon was studied by spin trapping method. The NO status of the wound tissue was investigated with EPR by following the formation of paramagnetic mononitrosyl complexes with iron-diethyldithiocarbamate, or with the heme groups in hemoglobin or myoglobin. For the first 5 min after a gas treatment with the exposure of 60s, detectable NO levels in the affected tissue were slightly lowered with respect to untreated controls. At subsequent times, treated tissues showed the formation of large quantities of nitroso-iron complexes: At 30-40 min after gas exposure, their levels were nearly two orders of magnitude higher than soon after (15 s-5 min) the exposure. The data demonstrate that the accumulation of nitrosyl-iron complexes reflects a sharp rise in endogenous NO production inside the affected tissue. Paradoxically, the beneficial effect of gaseous NO treatment can be mediated by the formation of limited quantities of peroxynitrite due to the reaction between exogenous NO and superoxide anions generated in high amount in wound tissue. This peroxynitrite has a strong prooxidant effect and can activate various antioxidant systems which diminish the amount of superoxide anions in wound tissue. The reduced superoxide levels allow to increase the contents of endogenous NO in gas-treated tissues. Therefore, the beneficial action of the treatment is attributed to enhanced NO bioavailability.