Dose-dependent effect of plasma-chemical NO-containing gas flow on wound healing. An experimental study

Abstract Background It is known that exogenous nitric oxide (NO) has a bactericidal effect, activates proliferation of fibroblasts, enhances angiogenesis and collagen synthesis, accelerates maturation of granulation tissue. Objective The purpose of this research was to study the dose-dependent therapeutic effect of nitric oxide (NO) in NO-containing gas flows (NO-CGF) applied to the wound surfaces. Methods The experiment was performed in 36 white Wistar rats with full-thickness skin wounds with an area size of 3 cm2. We used Plason device modified with an experimental plasma-chemical generator of nitric oxide (manipulator) for the following parameters of NO-CGF in the wound surface area: mass flow rate of nitric oxide 2.0 mg/s, axial gas flow velocity 9 m/s, nitric oxide content 1340 ppm, nitrogen dioxide content 108 ppm, gas flow temperature 39°C. Each group included 6 animals. The mass of nitric oxide delivered to the wound varied by the exposure time of 15, 30, 60, 120 and 360 seconds and was 30, 60, 120, 240 and 720 mg, respectively. Wounds were left untreated in the control group. Wound tissues were excised 4 days after the operation and studied with histological, semi-quantitative and morphometric methods. Results Histological analysis revealed beneficial effects of NO therapy on wound healing, including reduction of microcirculatory disorders and exudate volume and acceleration of fibroblast proliferation and collagen synthesis. We proved that the most effective stimulation of the wound healing process occurred with a duration of exposure of 120 and 360 seconds (integral mass doses of NO on the wound surfaces were 240 mg and 720 mg, relative mass doses of NO per wound areas were 80 mg/cm2 and 240 mg/cm2, respectively). We did not identify the overdose phenomena after prolonged exposure of the wound to NO. Conclusion Our results are important for further improvement of the technique and the standardization of NO-therapy for the treatment of wounds, inflammatory and destructive processes in clinical practice.