RU2688722C1 - Apparatus and method for experimental study and expansion of time boundaries of superdeep hypothermia - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: group of inventions relates to medical equipment. Device for studying resistance of mammals to super-deep hypothermia and expansion of limit time limits of animal's staying in state of super-deep hypothermia includes platform for fixation on back of tested animal, plastic bath, in which there is a platform, artificial ventilation system, mechanism of external massage of heart and lungs, through an external heart and lungs massage control unit connected to a heart and lung massage frequency control system comprising a needle electrode, a temperature sensor, through corresponding signal amplifiers connected to the interface, control unit of external cardiac and pulmonary massage mechanism connected to interface, and computer connected to interface by data transfer bus. Mechanism of external massage of heart and lungs is installed with possibility of individual adjustment for specific animal so that its lugs pressed on side areas of animal's thorax surface, and includes a frame arranged on the platform, a vertical guide fixed in the upper part of the frame and a rod movable inside it, having the possibility of transferring reciprocal movements to the left and right two-stage hinged drive for controlling the first and second horizontal rods, on which the said lugs are mounted. Disclosed is a method of studying resistance of mammals to superdeep hypothermia, which causes cardiac arrest, and expansion of limit time limits of animal in state of super-deep hypothermia.EFFECT: technical result consists in enabling analysis of animals with different standard sizes.3 cl, 5 dwg

Description

Technical field

The invention relates to the field of experimental medicine, in particular to disaster medicine. The present invention relates to a device and method for studying the resistance of mammals to hypothermia, allowing also to increase the ability to survive in conditions of artificially formed long-lasting, ultra-deep hypothermia, accompanied by a significant decrease in physiological activity, up to a stop in cardiac activity.

Prior technical level

Submarine accidents convincingly demonstrated the need to create effective ways to counteract the development of ischemic conditions in conditions of oxygen deficiency. One of such methods is the formation of a deep or super-deep hypothermia in animals or humans (the surface is isolated - 32-35 ° C, moderate - 28-32 ° C, deep -20-28 ° C and ultradeep - 20 ° C and below the hypothermia stage ), which achieves a significant reduction in heart rate, and then complete reversible cardiac arrest (reversible clinical death).

There is a known problem related to the increase in cooling resistance of mammals, which they are trying to solve by pre-activating the biochemical processes of mammals prior to their deep cooling [1, 2].

It is known that hypothermia is created in surgical practice when organs are cooled (during heart and brain operations). For this purpose, part of the organs are usually cooled and the whole body of the mammal is not subjected to hypothermia. To increase the resistance of humans and animals to hypothermia, drugs are used [3].

Also known technical solutions that use tools that increase the body's resistance in the posthypothermic period [4].

In the framework of the study of ultradeep hypothermia of animals, the study of permissible limiting values of hypothermia was carried out using external cooling of the whole animal's body [5]. Maximum hypothermia was achieved using external cooling with ice water (0 ° C) without the use of hypercapnic hypoxia and pharmacological preparations. At the same time, the animal had a state of clinical death after cardiac arrest. The duration of the period of recovery from the state of clinical death was investigated and a search was made for the optimal rate of warming of the body, providing the possibility of recovery.

The verification of the published data showed that the shortcoming of the described method is a short period of clinical death, after which the contractile activity of the heart and the general vital activity of animals can still be restored. In cases where warming up of animals after cardiac arrest begins after 20 minutes, and the total duration of clinical death (the time interval from cardiac arrest until the onset of heart contractions) does not exceed 30 minutes, the probability of a complete recovery of the vital activity of rats is 96%. A later start of warming up chilled rats, when the duration of clinical death exceeds 50-60 minutes, always leads to the death of animals.

However, there are a limited number of methods and devices for studying the behavior of mammals during the formation of hypothermia, for the therapeutic treatment of hypothermia in animals, and also for the withdrawal of mammals from conditions associated with cardiac arrest.

It is known that in the treatment of cardiac arrest, devices for ventilation of the lungs and devices for internal and external massage of the heart and lungs are widely used. In the patent of the Russian Federation № RU288861 "Resuscitator" [6] describes a device designed for external massage and forced ventilation during cardiac arrest. The device includes a housing with structural elements of patient fixation, an external heart massage mechanism with massage force regulators and control devices, a breathing mask with an oxygen supply system. The device further comprises the ability to automatically turn off the resuscitator at the moment when the patient has a pulse wave and the ability to monitor the pulse wave.

Known US patent No. US7226427 [7], which describes a device in which the massage of the lungs and heart is carried out using mechanical effects on the Central part of the chest simultaneously with the flow of gas into the lungs. In the patent of the Russian Federation No. RU2194488 [8], a device is described in which the chest is squeezed along the entire perimeter of the chest with the help of belts.

U.S. Pat. No. 5,590,820 [9] describes a device that includes two or more chest compressors, preferably inflatable bladders, that form pressure from above on the lungs and on the side surfaces of the lungs, increasing the pressure in the respective areas located in the jacket structure.

Known application for US patent No. US20150272822 [10], which describes the combined effect of mechanical effects on the central part of the chest and the possibility of cooling the side surfaces of the patient by passing coolant or gas through pillows installed on both sides and adjacent to the sides of the patient.

However, in order to investigate the capabilities of the mammalian organism under conditions of ultradeep hypothermia, it is necessary to ensure the cooling of the entire animal at high speed. This is necessary to simulate the conditions that occur when, for example, a person hits, in a catastrophic situation in situations involving rapid cooling.

In the course of the experiment, it is best to use cold water on an animal to cool the whole body. In this case, the application of known technical solutions for the manufacture of resuscitation devices for cardiac arrest is very problematic. Devices that use inelastic belts are difficult to maintain and can change their properties when working in a fluid. Devices in which compression of the chest occurs in its center is not optimal for small animals, which include mice and rats, because their chest is not across, but stretched along the body.

The main objective of the present invention is the creation of a method and device for the experimental study of the processes of deep hypothermia and cardiac arrest in laboratory animals, as well as the expansion of the limiting time limits of ultra-deep hypothermia.

In order to solve this problem, the aim of the present invention is to develop a device that uses a mechanism for external massage of the heart and lungs of mammals, taking into account their anatomical features.

Another aim of the invention is to develop a device for massage, working in the conditions of immersion in a liquid medium with the possibility of obtaining reproducible results when testing a large number of experimental animals.

The technical result of the use in the present invention, the mechanism for external massage of the lungs and heart is the improvement of performance characteristics due to the implementation of the possibility of research with different sizes of animals, simplifying the design by reducing the total number and types of elements that make up the hinge-lever mechanism, improving reliability and a resource of work due to simplicity of a technical solution.

Summary of Invention

One aspect of the invention is a device for studying the stability of mammals to ultradeep hypothermia and expanding the limiting time limits for an animal in this state consisting of a platform on which a test animal is fixed on its back, a plastic bath, an artificial ventilation system, a system for monitoring the temperature and frequency of an animal's heartbeat. , which includes a needle electrode, a temperature sensor, through the appropriate signal amplifiers connected to the interface, interface and computer ep. The device additionally contains a mechanism for external massage of the heart and lungs, which is connected through the node controlling the mechanism to the system for controlling the frequency of the massage of the heart and lungs. In this case, the reciprocating movement of the vertical rod of the mechanism is capable of being transmitted to the left and right two-stage articulated actuators for the simultaneous oncoming movement of the first and second horizontal rods with their legs installed to transfer pressure from the vertical rod through the hinges and legs to the sides of the animal for the implementation of an external massage heart and lungs, where the mechanism for massage is located on the platform above the animal in such a way that its legs press on the side areas of the body the chest of the animal, with the possibility of external massage of the heart and lungs.

Another aspect of the invention is a method for studying the resistance of mammals to ultradeep hypothermia and the expansion of the limiting time limits for an animal in this state. The animal is fixed on the platform in a supine position, intubated and artificially ventilated, and the heart rate and rectal body temperature are recorded. Above the animal place the mechanism of external massage of the heart and lungs, with the ability to move the device to implement individual settings for a particular animal. Place the platform with the placed animal on the bottom of a plastic bath, in which water is circulated at a temperature of 1 ° C. The intensity of artificial lung ventilation decreases with decreasing rectal temperature. Upon reaching a heart rate of up to 2-3 cuts per minute, include the mechanism of external massage of the heart and lungs for a pulsating mechanical effect on both sides of the animal in the lung area. In this case, artificial lung ventilation and indirect heart massage are performed during the entire period of cardiac arrest. According to the heart rate, the boundary is determined after which the animal leaves the state of clinical death when it is warmed. The intensity of artificial ventilation of the lungs is gradually increased in the process of warming as the rectal temperature rises, the heart's own work starts and the heart rate increases.

List of figures

The invention will now be explained in more detail with reference to the attached drawings, which show various embodiments.

FIG. 1. Block diagram of the device.

FIG. 2. Appearance of the mechanism for external massage of the heart and lungs.

3. Cooling and warming up of rats, the duration of clinical death did not exceed 30 minutes. The length of time from cardiac arrest to the onset of warming did not exceed 15 minutes. FIG. 3A shows the dynamics of rectal temperature in the process of cooling-warming. FIG. 3B shows the dynamics of heart rate (HR) in the process of cooling-warming.

FIG. 4. Cooling and warming up rats without using the device for indirect heart massage. The duration of the period from cardiac arrest to the onset of warming exceeded 40 minutes. FIG. 4A shows the dynamics of rectal temperature in the process of cooling-warming. FIG. 4B shows the dynamics of heart rate (HR) in the process of cooling-warming.

FIG. 5. Cooling and warming up of rats with the use of the device for indirect heart massage. The duration of the period from cardiac arrest to the onset of warming exceeded 40 minutes. The duration of reversible clinical death was about 50 minutes. FIG. 5A shows the dynamics of rectal temperature in the process of cooling-warming. FIG. 5B shows the dynamics of heart rate (HR) in the process of cooling-warming.

Description of the invention

The block diagram of the device is shown in FIG. 1. The described device contains: a platform 1 on which the test animal 2 is fixed on its back, a plastic bath 3, a mechanism for the external massage of the heart and lungs 6; artificial ventilation system, which includes a cylinder 15 with gas, a crane 16, a receiver 17, a three-way valve 18; control system of the frequency of massage of the heart and lungs, which includes: needle electrode 4, temperature sensor 5, signal amplifiers 10 and 11, node 9 controls the mechanism 8, interface 13, bus 7 data transmission, computer 14.

FIG. 2 shows the appearance of the mechanism for massage. The mechanism of external massage of the heart and lungs 6 is made on the basis of an inverted V-shaped frame, which is placed on the platform 1 above the working area in which the animal 2 is fixed. In the upper part of the V-shaped frame there is a vertical guide 23 inside which the vertical stem 24 moves. parts of the rod fixed axis 25, which is pivotally connected: the upper part of the first left lever 26 and the first right lever 27. The lower part of the first left lever 26 is pivotally connected to the upper part of the second left lever 28, and the lower part of the first right lever 27 is pivotally connected to the upper part of the second right lever 29. The central parts of the lower levers 28, 29 are mounted on additional axes 30 and 31 with the possibility of their rotation. The lower parts of the second left 28 and second right 29 levers, respectively, fit into the grooves of the left horizontal rod 32 and right horizontal rod 33 with the ability to transfer the vertical movement of the rod 24 through the hinge joints of the levers 26-29 to the horizontal movement of the rods 32 and 33 installed in the guides 34 and 35. On the inner ends of the rods 32 and 33, legs (pushers) 36 and 37 are fixed symmetrically relative to each other.

The method for studying the resistance of mammals to ultradeep hypothermia, causing cardiac arrest and expanding the limiting time limits for an animal in a state of ultradeep hypothermia, includes the following operations. The animal is fixed on the platform in a supine position, intubated and artificially ventilated. Needle electrodes are attached to the paws to register the heart rate, a temperature sensor is inserted into the body to register the rectal temperature. Above the animal place the mechanism of external massage of the heart and lungs, with the ability to move the device to implement individual settings for a particular animal. Place the platform with the placed animal on the bottom of a plastic bath, in which water is circulated at a temperature of 1 ° C. Rectal temperature and heart rate are measured and the intensity of mechanical ventilation is decreased as rectal temperature decreases. According to the heart rate, the boundary is determined after which the animal leaves the state of clinical death when it is warmed.

With a decrease in the cooling rate of the heart rate to 2-3 contractions per minute, include the mechanism of external massage of the heart and lungs for mechanical effects on both sides of the animal in the lung area and carry out an indirect massage of the lungs and heart. In this case, artificial lung ventilation and indirect heart massage are performed during the entire period of cardiac arrest. The intensity of artificial ventilation of the lungs is gradually increased in the process of warming as the rectal temperature rises, the heart's own work starts and the heart rate increases.

The device works as follows. Under ether anesthesia, animal 2 is fixed on platform 1 in a supine position. The animal is intubated to perform artificial ventilation of the lungs through a hose 19, which is connected through a three-way valve 18 and hose 20 to an artificial respiration system. The valve 18 controls the selenoid 21 by a signal from the output of the interface 13. On the paws of the animal fix needle-shaped electrodes 4 for recording heart rate and rectally enter the temperature sensor 5 for recording the body temperature. Above the animals set the mechanism of external massage of the heart and lungs 6, placed on the V-shaped frame. Bring to the side surfaces of the animal 2 legs 36 and 37, which are made with the possibility of regulating the massage force. Platform 1 together with rat 2 is placed in a plastic bath 3. Circulating water supplied from thermostat 22 is supplied and having a temperature of 1 ° C at the first stage for deep supercooling of the animal's body to a temperature of 5-8 ° C.

The rectal temperature of animal 2 is controlled by a temperature sensor 5 connected through amplifier 11, the output of which is fed through interface 13 and bus 7 to computer 14. As the rectal temperature decreases, the intensity of mechanical ventilation is reduced by controlling the receiver 17 manually or programmed from a computer (FIG. 1 connection of the receiver with the computer is not shown). Fully artificial ventilation is not disabled even after the final cardiac arrest.

Heart rate is controlled using a needle electrode 4, which is connected to the amplifier 10, the output signal of which is fed through the interface 13 and bus 7 to the computer 14. The heart rate decreases simultaneously with a decrease in rectal temperature, and upon reaching 10 ° C, only occasional reductions are observed hearts. At this moment (about 10 ° C), a command from computer 14 via bus 7, interface 13 to the input of control unit 9 receives a signal that is converted in mechanism 8 to reciprocating movements of rod 24 located in the mechanism of external massage of the heart and lungs 6. Through the hinge joints of the levers of the mechanism fixed on the V-shaped frame, the movement of the stem 24 is converted into reciprocating movements of the right 37 and left tab 36, which carry out periodic pressure on both side surfaces in the side regions of the animal’s lungs. At a temperature of 9-8 ° C, the own contractions of the heart completely stop and clinical death occurs. Blood oxygenation continues during the period of clinical death, since the air supply through the hose 19 is carried out using an artificial ventilation system, and artificial blood circulation during clinical death is supported by an external heart and lungs massage mechanism 6.

Depending on the experimental conditions, warming begins in the range from 15 to 45 minutes after the onset of clinical death. The rats are heated by gradual programmed heating of the water in the thermostat 22 and the bath 3, in which the experimental animal 2 is located. The heating programming is possible under the control of the computer 14 through the thermostat control unit (not shown in Fig. 1) or manually setting the heating rate on the thermostat 22. The mechanism of external massage of the heart and lungs 6 is disabled by a command from the control unit 9, the input of which is connected to the output of the interface 13 connected to the computer 14. The shutdown command is formed after start own heart rate, information on which is input to the amplifier 10 with the needle electrode 4 installed in the paw of the animal and through the communication interface 13 enters into the computer 14. Typically, the reduction in heart rate during heating is detected at the rectal temperature 9-10 ° C. Next, record the duration of clinical death, which is calculated from the time of complete cardiac arrest during cooling to the reappearance of heart contractions during warming. The intensity of artificial ventilation of the lungs gradually increases with increasing rectal temperature and an increase in the number of heartbeats per minute using the receiver 17, which can be controlled using a computer (not shown in Fig. 1) or in manual mode.

Example 1. Achieving ultra-deep hypothermia when cooling laboratory rats without a heart and lungs massage.

The rat, which is under ether anesthesia, is fixed on the operating table in the supine position. The animal is intubated to perform artificial ventilation of the lungs, needle electrodes are attached to the paws to record the heart rate, and a temperature sensor is inserted to register the rectal temperature. For cooling, the rat is completely placed in a plastic bath with circulating water having a temperature of 1 ° C.

The intensity of artificial ventilation of the lungs is reduced with decreasing rectal temperature, and at a temperature of 10 ° C completely shut off. As the rectal temperature decreases, the heart rate decreases, and when it reaches 9-8 ° C, the heart stops completely and clinical death occurs.

Warming the animal is carried out by controlled temperature increase. When the temperature reaches 8.5-9.0 ° C, the heart slowly begins to decline again, and at a temperature of 35 ° C, the heart rate is fully restored to normal. The period of time from stopping of heart contractions (9 ° С) during cooling to the reappearance of heart contractions (9 ° С) during warming up was taken to be the duration of clinical death.

FIG. 3 shows the curves of the change in the rectal temperature of rats cooled to 8 ° C, heated at a rate of 0.8 degrees per minute and restored to vital activity as a result of warming. In cases where warming up of animals after cardiac arrest begins after 15 minutes and the duration of clinical death (the time interval from cardiac arrest to the re-onset of heart contractions) does not exceed 30 minutes, the probability of complete recovery of vital activity of rats is 96%.

FIG. 4 shows the graphs of cooling and warming up of rats without the use of the device for indirect heart massage. The duration of the period from cardiac arrest to the onset of warming exceeded 40 minutes. FIG. 4A shows the dynamics of rectal temperature in the process of cooling-warming. FIG. 4B shows the dynamics of heart rate (HR) in the process of cooling-warming. The heart did not regain its activity as a result of prolonged cooling and the animal died.

Example 2. Achieving ultra-deep hypothermia during cooling of laboratory rats with a massage of the heart and lungs.

The animal is prepared for the experiment according to Example 1. A mechanism for external massage of the heart and lungs is established above the animal. Bring to the side surfaces of the animal legs, which are made with the possibility of regulating the massage force. The platform together with the rat is placed in a plastic bath and the circulating water supplied from the thermostat and having a temperature of 1 ° C is supplied for deep supercooling of the animal's body to a temperature of 5-8 ° C. As the rectal temperature decreases, the intensity of mechanical ventilation is reduced, but not completely disconnected, even after the final cardiac arrest. When the body temperature reaches 12 to 9 ° C, only episodic contractions of the heart occur. At this moment, on command from the computer, the mechanism of external massage of the heart and lungs is activated. At a temperature of 9-8 ° C, the heart’s own contractions cease completely and clinical death occurs. Blood oxygenation continues during the period of clinical death, since the air supply is carried out using an artificial lung ventilator. Extracorporeal circulation during clinical death is supported by the mechanism of external massage of the heart and lungs. Artificial ventilation of the lungs and artificial blood circulation are carried out during the entire period of clinical death caused by hypothermia, including the onset of warming animals. Warming begins in the range of 40 to 45 minutes after the onset of clinical death. Warming rats is carried out by gradual programmed heating of the water in the bath in which the experimental animal is located. Heart rate increases with the increase in the rectal temperature of the animal and when it reaches 35 ° C, cardiac activity is fully restored. At this point, the rat is removed from the water, freed from electrodes, tubes for artificial ventilation of the lungs and a thermometer. The final warming of the animals is carried out with warm air using a household hair dryer. Heated rats are placed in standard boxes for further maintenance and observation.

The results of the tests are shown in FIG. 5. With a duration of clinical death of more than 50 minutes, the control animals did not survive. In contrast, rats, which during the period of clinical death were subjected to an indirect cardiac massage, restored cardiac activity and general viability (Fig. 5B). The duration of the clinical death of these animals was about 60 minutes.

Thus, the proposed method allows two times (up to 60 minutes on average) to increase the duration of the reversible clinical death of laboratory rats cooled to ultra-low positive temperatures (up to 5 ° C), after which, when the animals warm up, their full recovery is still possible.

Industrial Applicability

The device mechanism for external massage of the heart and lungs, working in the conditions of immersion in a liquid medium, allows for the possibility of obtaining reproducible results when testing a large number of experimental animals. The use of such a device in combination with the use of artificial ventilation of the lungs allows, in conditions of reversible clinical death caused by profound hypothermia, when the heart’s own activity ceases, to continue to provide the body with oxygen-enriched blood.

Information sources

1. Mazalov V.K. et al. METHOD OF INCREASING THE STABILITY OF MAMMALS TO GENERAL COOLING, Auth. Certificate of the USSR № SU1520688 (08/27/1995).

2. BAZHANOV N.O. et al. MEANS FOR INCREASING THE RESISTANCE OF THE ORGANISM TO HYPOTHERMIA. The patent of the Russian Federation № RU2010569 (11.04.1991).

3. Doronin Yu.G. MEANS AND METHOD OF INCREASING HUMAN AND ANIMAL STABILITY TO HYPOTHERMIA BY ACTIVATING LIFE-IMPORTANT BIOCHEMICAL PROCESSES. The patent of the Russian Federation № RU2270008 (20.02.2006).

4. Bazhanov N.O. MEANS FOR INCREASING THE RESISTANCE OF THE ORGANISM IN THE POST-HYPOTHERMAL PERIOD. The patent of the Russian Federation № RU2268049 (05/20/2004).

5. P.V. Shcherbakov et al. Reversible deep hypothermia of the whole organism of rats // Bul. experiment biology and medicine. - 1989. - Vol. 107, No. 5, p. 543-545.

6. Sirotkina M.G. and others. "Resuscitator" Patent of the Russian Federation № RU288861 (00.00.1971).

7. STEEN STIG Systems and procedures for treating cardiac arrest. US Patent No. US7226427 (2007-06-05).

8. LEK Thomas and others. "DEVICE FOR COMPRESSION OF THE CHEST CELL WHEN STOPPING THE HEART (OPTIONS)". Of the Russian Federation No. RU2194488 (06.27.2000).

9. SCHOCK ROBERT et al. "Active compression / decompression cardiac assist / support device and method". United States No. TJS5490820 (1996-02-13).

10. United States №US20150272822 "Chest Compression Device". U.S. Patent No. US20150272822 (2015-10-01).

Claims (3)

1. A device for studying the resistance of mammals to ultra-deep hypothermia and expanding the limiting time limits for an animal in a state of ultra-deep hypothermia, including a platform for fixing the test animal on a back, a plastic bath containing a platform, an artificial ventilation system, an external massage mechanism for the heart and lungs, through the control unit of the mechanism of external massage of the heart and lungs connected to the control system of the frequency of massage of the heart and lungs, including the needle e Electrode, temperature sensor through appropriate signal amplifiers connected to the interface, control unit of the external heart and lung massage mechanism connected to the interface and computer connected to the data bus interface, while the external heart and lung massage mechanism is installed with the possibility of individual adjustment for a particular animal so that its legs pressed on the side areas of the chest surface of the animal, and includes a frame placed on the platform, fixed in the upper part of the frame and a vertical guide rod movable within it, having the ability to transfer the reciprocating motion to the left and right two-stage hinge actuator for controlling the first and second horizontal rods on which said foot installed. 2. A method of studying the resistance of mammals to ultra-deep hypothermia, causing cardiac arrest, and expanding the limiting time limits for an animal in a state of super-deep hypothermia, in accordance with which the device of claim 1 is used, where the animal is fixed on the platform in a supine position, intubated and carried out artificial ventilation of the lungs, fix the needle electrode on the paw of the animal to register the heart rate, insert a temperature sensor into the body to register the rectal temperature tours, place a platform with an animal placed on it at the bottom of a plastic bath with circulating water, reduce the intensity of mechanical ventilation as the rectal temperature decreases, measure rectal temperature and heart rate, and determine the beginning of clinical death according to heart rate data , after which the animal leaves the state of clinical death when it is heated, and in the event of episodic contractions of hearts occurring during the cooling process and carry out an additional pulsating mechanical effect on both side surfaces of the chest of the animal in the lung area and perform indirect heart massage, while artificial ventilation and indirect heart massage are performed during the entire period of cardiac arrest, while the intensity of artificial ventilation is gradually increased during the warming process and with the growth of rectal temperature, the launch of the heart’s own work and an increase in the heart rate, and the external massage they rasp after the start of warming up and starting the animals to have their own heart contractions. 3. The method according to p. 2, characterized in that the cooling of the animal is carried out with circulating water having a temperature of up to 1 ° C, when rectal temperature is reached from 5 ° C to 9 ° C, the coolant temperature is maintained in the same range until the animal starts to warm up .

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