A device for modeling hypoxia in rats

Abstract

The utility model relates to experimental medicine and can be used to simulate normobaric hypoxia in rats in order to evaluate the effectiveness of drugs for the treatment of pathological conditions accompanied by a decrease in oxygen delivery to tissues. A device for simulating hypoxia in rats includes a container, an inlet air flow outlet, a lid and a hose for connecting a gas analyzer, while the container is made of translucent plastic with the ability to accommodate a cage for everyday maintenance with rats, 455 mm long at the bottom and 540 mm at the top, 280 mm high, 310 mm wide at the base and 380 mm at the top, on one side surface of the container at a distance of 95 mm from the upper edge there are two ball valves for regulating the inlet air flow, built in through three-leaf cuffs measuring 32 × 50 mm at a distance of 100 mm,On the opposite side surface, at the bottom center, 25 mm from the bottom, there is an outlet air flow outlet with a nominal bore of 50 mm and a plastic plug with a diameter of 50 mm for regulating the outlet air flow, integrated through a transition three-petal cuff measuring 25 x 50 mm. The lid is 555 x 390 mm in size and equipped with a central hole with a diameter of 12 mm for a rubber hose with a nominal bore of 6 mm for connecting a gas analyzer. The use of the proposed device makes it possible to create and maintain the required oxygen concentration over any time interval, minimize stress in the experimental rats, which remain in their usual environment with food and water, and avoid direct contact between the researcher and the rodents, thereby eliminating the possibility of bites, scratches, and other injuries.

Description

[0001] The utility model relates to experimental medicine and can be used to simulate normobaric hypoxia in rats in order to evaluate the effectiveness of drugs for the treatment of pathological conditions accompanied by a decrease in oxygen delivery to tissues.

[0002] Tissue hypoxia accompanies obstructive diseases of the bronchopulmonary system, blood and cardiovascular pathologies, and various chronic inflammatory processes. Modern pharmacological developments offer a wide range of antihypoxic agents, the mechanism of action and safety of which require experimental study in laboratory animals, most often rats. Modeling hypoxia under experimental conditions allows for the partial or complete reproduction of corresponding changes in many organs and tissues. However, conditions should be created as close as possible to the pathogenesis of hypoxia and the rules of humane animal handling should be observed.

[0003] Several utility models have been proposed for simulating hypoxia in rats. "Device for Simulating Hypoxia in Small Laboratory Animals" (patent RU 178743 U1) consists of a sealed chamber, the body of which is an upside-down container, and the floor is perforated with holes 5-7 mm in diameter. The chamber contains a pressure gauge and a temperature sensor and is connected to a heating device, which is integrated with the air duct of a rotametric system. The device allows for regulation of the temperature and pressure of the supplied gas mixture. The disadvantages of this model include: 1) handling potentially explosive heated gas mixtures supplied under pressure; 2) stress that occurs in animals when placed in a new environment with rapidly changing oxygen concentrations.

[0004] Another model for simulating acute exogenous normobaric hypoxia without hypercapnia in small laboratory animals (patent RU 2 291 498 C1) is designed as a sealed container with a carbon dioxide absorber (soda lime) at the bottom and equipped with a pressure compensator in the form of an elastic balloon communicating with atmospheric air and a pressure sensor. The disadvantages of this device are: 1) contact of the animal with soda lime, which can cause damage to the skin, eyes, and mucous membranes; 2) reproduction of only acute hypoxia with a fatal outcome, which is completely uninformative for the analysis of changes characteristic of respiratory, circulatory, hemic, and tissue forms of hypoxia developing due to disease.

[0005] The closest prototype of the proposed device is the model described in the method for simulating normobaric chronic hypoxia (patent 2,739,675 C1), in which animals were placed in a sealed 1.2-liter container filled with air. The oxygen concentration in the inhaled air gradually decreased due to the natural absorption of oxygen during respiration. The container is equipped with two tubes, one for incoming and one for outgoing air flows, connected to a MAG-6-P-K multichannel gas analyzer (O2, CO2). The disadvantages of this model include the small volume of the container, which does not allow for simultaneous testing of several animals, stress when placed in a new environment, lack of access to water and food when simulating chronic hypoxia, which requires prolonged stay in an isolated chamber, and termination of the session when the oxygen concentration in the inhaled air reaches 10%.

[0006] The technical result of this utility model is the simulation of normobaric subacute and chronic hypoxia in rats without removing them from their daily cage, which eliminates the creation of stressful conditions for animals and direct contact between the researcher and the rodents, and also allows for the gentle regulation of the oxygen concentration inside the chamber and the conduct of experiments over various time intervals, preventing the death of the animals.

[0007] The technical result is achieved in that the device for modeling hypoxia in rats includes a container, an inlet air flow outlet, an outlet air flow outlet, a lid and a hose for connecting a gas analyzer, while the container is made of translucent plastic with the ability to accommodate a cage for everyday maintenance with rats, 455 mm long at the bottom and 540 mm at the top, 280 mm high, 310 mm wide at the base and 380 mm at the top, on one side surface of the container at a distance of 95 mm from the top edge there are two ball valves for regulating the inlet air flow, built in through three-petal cuffs measuring 32x50 mm at a distance of 100 mm, on the opposite side surface at the bottom in the middle at a level of 25 mm from the bottom there is an outlet air flow outlet with a nominal bore of 50 mm and a plastic plug with a diameter of 50 mm for regulating the outlet air flow, built in through a transition three-petal cuff 25×50 mm,and the cover is made with dimensions of 555×390 mm and is equipped in the middle with a hole with a diameter of 12 mm for a rubber hose with a nominal bore of 6 mm for connecting a gas analyzer.

[0008] The utility model is explained with figures.

[0009] Fig. 1 - general diagram of the device.

[0010] Fig. 2 - device diagram. Top view and bottom view.

[0011] Fig. 3 - diagram of the device cover.

[0012] Fig. 4 - diagram of side surfaces.

[0013] Fig. 5 - An example of using the device.

[0014] Fig. 6 - view of the device from the ball valves side.

[0015] Fig. 7 - view of the device from the branch side.

[0016] The device consists of a container made of translucent plastic, 455 mm long at the bottom and 540 mm at the top, 280 mm high, 310 mm wide at the base and 380 mm at the top (Fig. 1, Fig. 2), with a lid of 555x390 mm (Fig. 3). To regulate the volume of incoming air, two ball valves with a nominal bore of 32 mm are built into the side at a distance of 95 mm from the upper edge of the container through transition three-petal cuffs measuring 32x50 mm at a distance of 100 mm from each other (Fig. 4, Fig. 5, Fig. 6). On the opposite side, at a distance of 25 mm from the bottom of the container (Fig. 1), a 50 x 87 mm outlet with a 50 mm diameter plastic plug is built in through a 25 x 50 mm transition three-petal cuff to regulate the air outlet flow (Fig. 4, Fig. 7).

[0017] A rubber hose with a nominal bore of 6 mm is located in the center of the container lid for connecting the Guard-101 "TORTES" gas analyzer (Fig. 3, Fig. 5). Alternatively, the gas analyzer can be placed inside the container and readings can be observed through the translucent walls of the container (Fig. 7).

[0018] For more reliable sealing, the edges of the container are sealed with KIM TEC 9×8 mm and 9×4 mm rubber seals.

[0019] The device is used as follows.

[0020] A ZoonLab #3 heat-resistant plastic cage, 425×265×150 mm, with a stainless steel mesh lid, a drinking bowl, and rats inside, is placed inside the container and closed with a lid (Fig. 5). The gas analyzer with an oxygen sensor can be located either on the mesh lid inside the container (Fig. 7) or connected to a rubber hose on the surface of the lid (Fig. 5). The gas analyzer readings are used to estimate the oxygen concentration inside the container, which gradually decreases due to the natural vital activity of the animals. When the oxygen concentration set for the experiment is reached, the ball valves on the side (Fig. 6), which are located at the level of the mesh lid of the animal cage, are fully or partially opened and, if necessary, the plug is removed from the branch on the opposite side (Fig. 7). After the oxygen concentration inside the container has stabilized, the system is left in a static position for the time interval required in the experiment.The proposed device allows for: 1) minimizing stress in experimental rats by keeping them in their familiar environment with food and water; 2) avoiding direct contact between the researcher and the rodents, thereby eliminating the possibility of bites, scratches, and other injuries; and 3) creating and maintaining the required oxygen concentration over any period of time. Additional advantages of the proposed device include:

[0021] 1. Lightweight and easy to transport (the 50-liter container with built-in components weighs 1900 grams). Stiffening ribs and finger grooves allow for comfortable grip and portability.

[0022] 2. The transparent case allows you to observe the experimental process from both above and from the sides.

[0023] 3. Animals have constant access to food and water.

[0024] Easy adjustment of air flow thanks to taps and plugs.

[0025] 5. Convenient to use gas analyzer with an oxygen sensor, which can be placed either inside the container, on the lattice lid of the animal cage, or attached to a rubber hose on the surface of the container lid.

[0026] 6. Minimum material costs in the manufacture of the structure.

[0027] Bibliography:

[0028] 1. Patent for Utility Model No. 178743 U1 Russian Federation, IPC G09B 23 / 28. Device for modeling hypoxia in small laboratory animals: No. 2017141221: declared 27.11.2017: published 18.04.2018 / A.A. Vinogradov, I.V. Andreeva, A.V. Pavlov [et al.]; applicant Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after Academician I.P. Pavlov" of the Ministry of Health of the Russian Federation.

[0029] 2. Patent for utility model No. 2291498 C1 Russian Federation, Device for modeling acute exogenous normobaric hypoxia without hypercapnia in small laboratory animals: No. 2005112394 / 14: declared. 25.04.2005: published. 10.01.2007 / A.V. Evseev, M.A. Evseeva, D.V. Sosin; State Educational Institution of Higher Professional Education "Smolensk State Medical Academy of the Federal Agency for Healthcare and Social Development".

[0030] 3. Patent for Utility Model No. 2739675 C1 Russian Federation, IPC A61D 3 / 00. Method for modeling normobaric chronic hypoxia: No. 2020123722: declared 17.07.2020: published 28.12.2020 / Yu.A. Marsyanova, V.I. Zvyagina; applicant Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after Academician I.P. Pavlov" of the Ministry of Health of the Russian Federation.

Claims

A device for modeling hypoxia in rats, comprising a container, an inlet air flow outlet, an outlet air flow outlet, a lid and a hose for connecting a gas analyzer, characterized in that the container is made of translucent plastic with the ability to accommodate a cage for everyday maintenance with rats in it, 455 mm long at the bottom and 540 mm at the top, 280 mm high, 310 mm wide at the base and 380 mm at the top, on one side surface of the container at a distance of 95 mm from the top edge there are two ball valves for regulating the inlet air flow, built in through three-leaf cuffs measuring 32x50 mm at a distance of 100 mm, on the opposite side surface at the bottom in the middle at a level of 25 mm from the bottom there is an outlet air flow outlet with a nominal bore of 50 mm and a plastic plug with a diameter of 50 mm for regulating the outlet air flow, built in through a transition three-leaf cuff of 25x50 mm,and the cover is made with dimensions of 555×390 mm and is equipped in the middle with a hole with a diameter of 12 mm for a rubber hose with a nominal bore of 6 mm for connecting a gas analyzer.

Images