Microcirculatory effects of systemic metabolic correction with reactive oxygen species: An experimental study

Abstract

Introduction: The purpose of this study is to estimate microcirculation changes under systemic (intraperitoneal) administration of ozonized saline. Methods: For this study, we formed four equal groups of Wistar male rats (n = 10 per group). Rats of first (control) group was intraperitoneally injected with non-ozonized sterile saline solution (daily administration volume — 1 ml.) during 30 days. Animals of other groups (n = 10 for second, third and fourth groups) received 30 intraperitoneal infusions (1 ml/day) daily with ozonized saline solution (saturating ozone concentration for indicated groups — 3000, 10000 and 40000 mcg/l, ozone dose per procedure — 0.75, 2.5 and 10 mcg, respectively). Technology of the Laser Doppler Flowmetry (LDF) along with ``LAKK-02'' device (Moscow, Russia) was used for complex estimation of skin microcirculation state. This technology allows us to study blood flow intensity in skin microvessels at the first and thirty-first days of the experiment. We also can estimate regulatory mechanisms of microcirculation support and the presence of shunt paths of the microcirculation. Results: We studied the dose-dependent response of microcirculation on ozone infusions in chronic experiments. We found that long-lasting course (30 procedures) of intraperitoneal administration of ozonized sodium chloride solution provides an increase in the level of microcirculation index compared to that of the control (injections of nonozonized saline solution), regardless of the applied dose of ozone. At the same time, the level of the microcirculation response was directly determined by the introduced amount of ozone, and we fixed non-linear dependence on it. Our study allowed us to show that only low doses of ozone (0.75 mcg/day) have proadaptive effects on the microcirculatory bed. This was shown both in the dynamics of the microcirculation index and the state of regulatory mechanisms. Middle ozone dose (2.5 mcg/day) also caused the stimulation of blood flow in small vessels, though this was predominantly through other mechanisms (neurogenic components). The most negative reaction of microcirculation was observed for high ozone dose (8 mcg). Conclusion: Despite the activation of microcirculation observed in this case, we have identified that the mechanism was primarily through the respiratory component regulation and via formation of "steal syndrome" in the tissue.