Журнал «Медицина неотложных состояний» 1 (56) 2014

Introduction. Common pathogenetic link of any of the critical state is hypoxia. Reperfusion and reoxygenation of injured tissues in process of treatment of terminal states is often accompanied by the progression of ischemic cell damage. Therefore, preventive issues and drug therapy of acute hypoxia are an important biomedical problem.

One of the most promising directions in solving this problem is to find new antihypoxants among original elementoorganic, including coordination compounds. To such kind of potential pharmacological agents belong complex compounds of germanium.

Earlier in screening studies on the model of hypoxic hypoxia with progressive hypercapnia was revealed a pronounced antihypoxic activity of coordination compound of germanium with diethylene triamine pentaacetic acid and potassium (VITAGERM-3).

Goal of research was to evaluate in dynamic an ability of VITAGERM-3 to regulate acid- base balance in animals under hypoxic condition in an enclosed space.

Materials and techniques. The studies were performed on 72 adult white outbread rats of both sexes in the laboratory of the Pharmacology Department of SE "Lugansk State Medical University".

As an experimental model was chosen a pathological process that develops in animals in a closed space. Modeling of hypoxia with progressive hypercapnia was performed by placing the rats in the isolated glass containments (10 dm³), which were turned upside down and placed into a tray with water in order to prevent airing. Exposure time was 30 min. All animals were divided into 4 groups: intact ("healthy" rats), control (hypoxia), experimental (hypoxia + VITAGERM-3) and reference (hypoxia + mexidol). The animals of experimental group were injected intraperitoneally VITAGERM-3 in the previously developed dose regimen: 49 mg/kg 36 min prior to modeling the hypoxia of an enclosed space. As a reference substance was chosen mexidol that was administered to rats in a dose 100 mg/kg 36 min prior to the development of the hypoxic syndrome. Animals in the control group received solution of sodium chloride in the same regimen.

In order to determine the state of acid-base balance were taken samples of venous blood of rats with heparinized syringe from the femoral vein in 1 and 6 hours after removal from the containment. Measurements of the parameters of acid-base balance were performed on the digital analyzer of electrolytes and blood gases OPTI CCA (production OPTI Medical Osmetch, USA). Parameters are following: negative logarithm of the hydrogen ions (pH); pH adjusted on temperature (pH[T]); partial pressure of carbon dioxide (pvCO₂) partial pressure of oxygen (pvO₂), the total concentration of carbon dioxide (tCO₂); concentration of bicarbonate ion (HCO₃^–) blood oxygen saturation (SvO₂); standard bicarbonate (SBC); excess (deficit) bases (BE) .

The experimental data were statistically processed using the Student t-test.

Results. Found that the pH of the blood of animals of all groups is within the physiological range for rats (7.28–7.34). However, it should be remembered that the pH values ​​close to normal do not exclude violations of acid-base balance, which can be compensated by buffer systems of blood. Therefore, further we did a complex analysis of other parameters of acid-base balance in studied experimental conditions.

Particular attention is paid to the analysis of the dynamics of changes of venous blood gas composition, reflecting the level of metabolism and blood flow rate in the tissues. It has been established that in conditions of hypoxia of an enclosed space in the control group at the first stage of observation there was a significant decrease of the partial pressure of oxygen in the venous blood. Moreover, pvCO₂ were increased to 57,02 ± 3,80 (P < 0,05). Such blood gas state is equivalent to respiratory acidosis. Later, with restoration of gas exchange in rats in 6 hours of study, the pH of blood got a character of acidosis, but the BE took negative values (P < 0,05), pvO₂ increased to the level of the lower limits of intact animals (P < 0,05) and pvCO₂ decreased in 2,5 ± 1,36 times. These changes are characteristic for metabolic acidosis with respiratory compensation. Reoxygenation of tissues in early posthypoxic period is associated with depletion of compensation systems serving to maintain extracellular pH values for most of the metabolic processes of the body.

In the experimental group of animals after administration of VITAGERM-3 on the first phase of the study acid-base balance had the character of compensated respiratory changes. The pH of blood was on a baseline (P > 0,05). PvSO₂ was significantly (P < 0,05) increased.

Experimentally proven that in the experimental group of animals for maintaining of metabolic processes oxygen uptake by tissues already on the 1 hour of reoxygenation was increased, as evidenced by a decrease of the SvO₂ on 14 % (P < 0,05).

At the next stage of the study changes of acid-base balance were limited to respiratory component and compensated metabolic processes. Active removal of CO₂ from the body continued and it level throughout the study had a significant difference from the intact animals. SvO₂ was on a baseline. An important argument for compensation are changes in level of standard blood bicarbonate (SBC), the concentration of which is close to the diagnostic value of HCO₃^–. These figures in 6 hours after severe hypoxia turned back to the level of the intact group.

Conclusions. Thus, the results of study of acid-base balance of venous blood in normal animals and in the early period of reoxygenation after hypoxic hypoxia on the background of hypercapnia under prophylactic administration of an original coordination compound of germanium VITAGERM-3 convincingly demonstrate the ability of this compound to stabilize the processes of absorption of oxygen by tissues due to activation of the main buffer systems of blood plasma, as well as optimizing the level of metabolic processes by reducing the rate of O₂ extraction from the blood.