Local Hypothermia Research Articles

Effects of Local Hypothermia on Limb Viability in a Swine Model of Acute Limb Ischemia During Prolonged Damage-Control Resuscitation.

New strategies are needed to mitigate further tissue injury during traumatic limb ischemia in cases requiring damage control resuscitation (DCR). Little is known about the pathophysiology and injury course in acute limb ischemia (ALI) with DCR in polytraumatized casualties. We therefore investigated the effects of therapeutic limb hypothermia in a swine model of ALI and DCR. Fifteen swine underwent a published 6-hour DCR protocol of hemorrhage and then resuscitation. After hemorrhage, animals were randomized to 5oC or 15oC cooling of one hindlimb; the contralateral limb serving as an uncooled control. Physiologic variables, limb temperature, and limb tissue metabolites (glucose, lactate, and pyruvate) were measured throughout the DCR protocol. Muscle and nerve biopsies were obtained after the 6-hour protocol. Lactate and pyruvate levels were significantly lower in the cooled limbs than in the uncooled control limbs but did not differ between the 5oC and 15oC groups. Tissue glucose levels did not differ between the 5oC group, the 15oC group, and controls. Mean histologic muscle score was significantly higher in the 5oC group than in controls (p = 0.03). Mean nerve histology scores did not differ between the 5oC and paired control limbs, or between the mean muscle and nerve histology scores of the 15oC and paired control limbs. Cooling to 15oC significantly reduced local tissue metabolites compared to paired controls, while producing no significant increase in histologic damage, whereas cooling to 5oC increased histologic muscle damage. These results suggest an approach to prevention of ischemic injury through local hypothermia but warrant further functional testing.

Can internal cooling radiofrequency catheters with local hypothermia eliminate the need for tumescent anesthesia? A single-center, retrospective, observational study.

Background: Tumescent anesthesia not only prolongs the operation time but also induces postoperative pain, bruising, and swelling. This study investigated the effectiveness and safety of tumescentless RFA using an internal cooling system with a VENISTAR catheter and local hypothermia. Methods: We retrospectively analyzed patients who had undergone RFA for above-knee (AK) great saphenous vein (GSV) between March 2023 and November 2023. We compared the efficacy and safety of tumescentless RFA between group T (conventional tumescent group, n = 50) and group N (non-tumescent group, n = 59). Results: The operative time was shorter in group N than in group T (group N: 31.37min, group T: 42.31min, p < .01), with no severe adverse events occurred in either group, such as endovenous heat-induced thrombosis or deep vein thrombosis. Postoperative pain (Group N, 0.53% vs Group T, 0.52%; p = .86), postoperative complications such as bruising (Group N, 6.78% vs Group T, 4%; N= .34) and paresthesia (Group N, 1.7% vs Group T, 6%; p = .27) showed no significant difference between the two groups on postoperative day 10. Conclusion: Tumescentless RFA with internal cooling and local hypothermia shows promising results with minimal complications. This novel approach represents a recent advancement in endovenous RFA that omits additional tumescent anesthesia.

A mathematical model of a thermoelectric device for local hypothermia of the knee joint

A mathematical model of a thermoelectric device for local hypothermia of the knee joint

Evaluation of Neuroprotective Effects of Local Hypothermia in a Porcine Spinal Cord Injury Model

Abstract The goal of this study was to assess the therapeutic potential of a 5-hour local spinal cord (SC) hypothermia by 4 °C saline on preservation of SC tissue at the injury epicentre and 3 cranial and caudal 10 mm long SC segments in a porcine experimental model of spinal cord injury (SCI). The SCI was inflicted through L3 laminectomy by a metallic rod moved by a velocity of 30 mm.sec−1, and operated by a computer-controlled apparatus. A group of 15 female minipigs 5‒8-month-old weighing 28‒35 kg was randomly divided into 5 subgroups (each composed of 3 animals): 1) sham controls; 2) SCI by force 8N; 3) SCI by force 8N, 5-hour hypothermia; 4) SCI by force 15N; 5) SCI by force 15N, 5-hour hypothermia. After a 9-week survival period, the minipigs were in deep general anaesthesia transcardially perfused by 5000 ml of saline and fixed by 5000 ml 4 % neutral paraformaldehyde. White and grey SC matter damage was evaluated in specimens cut from the epicentre of injury as well as 3 cranial and 3 caudal 10 mm long SC blocks dyed according to Luxol fast blue (LFB) with cresyl violet (CV) protocol for light microscopic observations. The percentage of preserved SC white and grey matter was assessed in microphotographs and compared with data from sham controls (considered 100 %). The data were statistically evaluated by ANOVA test, the difference P ˂ 0.05 was considered significant. Results of the study suggest that 5-hour local cooling of the epicentre of SCI is well tolerated and facilitates the preservation of SC tissue integrity. Additional experimental and preclinical studies are necessary before introducing the method in practice.

Hypoxic irreversible brain cells damage, associated risk factors and antihypoxants

It is reported that in the final stage of many diseases the immediate cause of biological death in humans and warm-blooded animals is hypoxic irreversible damage to brain cells. This explains the fact that to prevent biological death in all critical conditions without exception, inhalation with breathing gases containing oxygen has long been successfully used. This is also why oxygenation of the blood is considered one of the main conditions for preserving human life in all critical situations and forms the basis of emergency medical care in the intensive care unit. However, inhalation of oxygen gas and increasing blood oxygen saturation should be carried out as early as possible, and more precisely - before the onset of the stage of hypoxic irreversible damage in brain cells. The fact is that after the onset of irreversible damage brain cells die even in the presence of oxygen. In this connection, the mechanisms of adaptation of the organism to oxygen deficiency play a great role for longer preservation of brain cells viability and human life in conditions of hypoxemia. In order to increase resistance to hypoxemia, antihypoxants are traditionally used. But they can preserve the viability of brain cells not always, but only if they are introduced into the body before the onset of hypoxic irreversible damage to brain cells and in the case of unused reserves of adaptation to hypoxemia in the body. Risk factors of hypoxic irreversible damage of brain cells are indicated, among which excessively long duration of hypoxemia and hyperthermia are emphasized. It is shown that the most important circumstance for the development of hypoxic irreversible damage of brain cells is not so much the degree of hypoxemia as the degree of hypoxia of brain tissue and its duration, which exceeds the period of human resistance to hypoxia. It has been shown that human resistance to hypoxia can be assessed using the Stange test. It has been reported that fever and local cerebral hyperthermia decrease, and hibernation and local cerebral hypothermia increase, the resistance of brain cells to hypoxia. In this regard, recommendations not only to eliminate fever and local inflammatory processes in the head, but also recommendations to reduce brain temperature are highly appropriate to improve resistance to hypoxia. It is pointed out that among the methods of local therapeutic hypothermia, targeted temperature management is the most advanced. In addition, it is reported that in recent years a new group of promising antihypoxants - alkaline solutions of hydrogen peroxide - has been created. It is shown that hydrogen peroxide is able to decompose very quickly into water and oxygen gas under the action of catalase, which is found in all tissues. The peculiarities of using alkaline solutions of hydrogen peroxide as antihypoxants we all have to study in the future.

Thermoelectric device for the treatment of panaritium by local hypothermia

Thermoelectric device for the treatment of panaritium by local hypothermia

Enhancing Liver Transplant Outcomes through Liver Precooling to Mitigate Inflammatory Response and Protect Mitochondrial Function.

Transplanted organs experience several episodes of ischemia and ischemia-reperfusion. The graft injury resulting from ischemia-reperfusion (IRI) remains a significant obstacle to the successful survival of transplanted grafts. Temperature significantly influences cellular metabolic rates because biochemical reactions are highly sensitive to temperature changes. Consequently, lowering the temperature could reduce the degradative reactions triggered by ischemia. In mitigating IRI in liver grafts, the potential protective effect of localized hypothermia on the liver prior to blood flow obstruction has yet to be explored. In this study, we applied local hypothermia to mouse donor livers for a specific duration before stopping blood flow to liver lobes, a procedure called "liver precooling". Mouse donor liver temperature in control groups was controlled at 37 °C. Subsequently, the liver donors were preserved in cold University of Wisconsin solution for various durations followed by orthotopic liver transplantation. Liver graft injury, function and inflammation were assessed at 1 and 2 days post-transplantation. Liver precooling exhibited a significant improvement in graft function, revealing more than a 47% decrease in plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, coupled with a remarkable reduction of approximately 50% in liver graft histological damage compared to the control group. The protective effects of liver precooling were associated with the preservation of mitochondrial function, a substantial reduction in hepatocyte cell death, and a significantly attenuated inflammatory response. Taken together, reducing the cellular metabolism and enzymatic activity to a minimum level before ischemia protects against IRI during transplantation.

Controlled local hypothermia in the complex treatment of patients with congenital anomalies of jaw development

Controlled local hypothermia in the complex treatment of patients with congenital anomalies of jaw development

Sex differences in skin microcirculatory vascular reactivity in experimental lipopolysaccharide-induced endotoxinemia

Bacterial lipopolysaccharide (LPS) plays a leading role in the development of a systemic inflammatory response and endogenous intoxication. However, the sex differences in the functional state of the microcirculatory bed in LPS-induced endotoxinemia have been poorly studied. Objective. To study the characteristics of skin microcirculatory vascular reactivity in experimental LPS-induced endotoxinemia in male and female rats. Material and methods. Modeling of endotoxinemia was performed by intraperitoneal injection of LPS of the cell wall of the bacterium Salmonella enterica to male and female Wistar stock rats. Two doses of LPS were used: 50 mg/kg and 10 mg/kg. We used laser Doppler flowmetry to evaluate skin perfusion before and after LPS injection, blood flow changes under test conditions with local contact hypothermia caused by a thermoelement. Results. 48 hours after LPS injection, a decrease in blood flow was observed, especially pronounced at a dose of LPS 50 mg/kg. During the test with local cooling of the skin, a change in the kinetics of the reaction was noted. Blood flow reduction was 75% (LPS 50 mg/kg) and 51% (LPS 10 mg/kg), statistically significantly different from the control groups. At the same time, the classic phenomenon of “cold vasodilation” observed in control rats was absent in all groups with the injection of LPS. Maximum perfusion after restoration of blood flow in females was achieved 3 times faster than in males (LPS 10 mg/kg). Conclusion. In experimental LPS-induced endotoxinemia, a dose-dependent decrease in skin perfusion was revealed. We obtained new data on the absence of pronounced “cold vasodilation” at local contact hypothermia. The results of the study indicate a violation of the mechanisms of neurogenic vasoconstriction and endothelium-dependent vasodilation, reflecting systemic disorders of microcirculation regulation. At the same time, the females showed a more positive dynamics of blood flow restoration in the test with local cooling of the skin, indicating a greater functional reserve and a more effective mechanism of autoregulation of the blood microcirculation system. A functional test with local contact cooling of the skin is highly informative for assessing vascular reactivity and preservation of the autoregulation mechanism of microcirculation in modeling endogenous intoxication

Hypothermia induced by bronchoalveolar lavage with perfluorocarbon liquids as a method for the treatment of the alveolar stage of toxic pulmonary edema. Experimental assessment

Introduction. The rapid development of the chemical industry in the Russian Federation is accompanied by an increase in the production and storage of highly toxic substances belonging to the group of pulmonotoxicantsare able to induce lung injury, the most severe form of which is toxic pulmonary edema (TPE). The treatment of TPE includes medication and respiratory therapy, but such a combination turns out to be insufficient, and therefore the development of new methods of treatment of the alveolar stage is an important task of modern medicine. One such approach is the use of therapeutic hypothermia, which can reduce the severity of TPE in general and the alveolar stage in particular. Recently, the use of various options for liquid ventilation of the lungs with perfluorocarbon (PFC) liquids for the induction of therapeutic hypothermia has attracted increasing attention from specialists. This article will present the results of an experimental assessment of the effect of hypothermia induced by BAL with PFC fluids on the course of the alveolar stage of toxic pulmonary edema. The study aims to determine the effect of hypothermia induced by bronchoalveolar lavage with a pre-cooled PFC liquid on the course of the alveolar stage of toxic pulmonary edema. Materials and methods. The authors conducted a study on male Wistar rats aged 4 months, weighing 200–220 g. TPE was modeled by intratracheal administration of 0.1 m HCl solution at a dose of 2 ml/kg. Specialists pre-injected atropine into the animals, then anesthetized, intubated with cannulas, injected a model substance and connected to a ventilator. After that, the animals were randomized by weight into two groups of 6 individuals each. In animals of the experimental and control groups, with a decrease in oxygen saturation (SpO2) below 80%, the researchers performed 2 procedures of bronchoalveolar lavage (BAL) with PFC liquid in a single dose of 2.0 ml / kg, with different temperatures. Perfluorodecalin was used as a PFC liquid. In the experimental group, the temperature of the PFC liquid during BAL was 0.5°C, in the control group — 38.0°C. Specialists recorded heart rate (HR), oxygen saturation, rectal temperature (Trect) and duration of survival. Results. Immediately after instillation of 0.1 M HCl solution, all animals showed a sharp decrease in SpO2 (from 97±1.3 to 64±11.5) and heart rate (HR), (from 269±8.7 to 123±24.5). Recovery of indicators was observed after administration of atropine sulfate. Over the next 25–30 minutes, the following signs appeared and subsequently intensified: a decrease in SpO2 below 80%, an increase in heart rate (HR) to 302±11.4 beats/min, the presence of wet wheezing in the lungs and the release of exudate from the endotracheal catheter. In response to the BAL, all animals showed an increase in SpO2 and a decrease in heart rate. So, in the control, in response to the BAL, SpO2 increased by 8.0±2.5%, and heart rate decreased by 21.0±5.4 beats /min. While in the experimental group there was an increase in SpO2, which was 11.0±3.1%, and a decrease in heart rate by 57.0±10.2 beats/min. At the same time, during the experiment, the researchers observed an increase in temperature in the control group by 0.08±0.02°C, and in the experimental group — its decrease by 0.70±0.07°C. The average survival time of animals in the control and experimental groups was 64.8±2.2 minutes and 91.2±5.9 minutes, respectively. Conclusion. The use of BAL PFC liquids with a low temperature makes it possible to increase the survival time of small laboratory animals in the alveolar stage of TPE due to the development of local and general hypothermia. The development of local hypothermia during BAL of the lungs makes it possible to remove a significant amount of edematous fluid, which, in turn, manifests itself in less pronounced respiratory and systemic hemodynamic disorders. Ethics. Studies involving laboratory animals were conducted in compliance with the following regulations: Helsinki Declaration of 2000 "On humane treatment of animals", Order of the Ministry of Health of the USSR No. 755 dated 08/12/1977 "Rules for carrying out work using experimental animals", Order of the Ministry of Health and Social Development of Russia No. 199n dated 04/01/2016 "On approval of the rules of laboratory practice". The research protocol was approved by the Ethics Committee of the Izmerov Research Institute of Occupational Health (Protocol No. 4 dated May 25, 2022).

Autophagy Behavior under Local Hypothermia in Myocardiocytes Injury.

Hypothermia and autophagy are critical regulators of cell homeostasis by regulating intra and intercellular cell communication. Myocardiocyte cryotherapy poses multiple cellular and subcellular effects on the injured cell, including upregulation of autophagy. Autophagy plays a crucial role in modifying cell metabolism by regulating downregulation, reducing reactive oxygen species production, and improving the natural cellular antioxidant defense system. Reduction of reactive oxygen species production and improving natural cellular antioxidant defense system. Therapeutic hypothermia ranges from 32-34°C in terms of local myocardiocyte cooling. Hypothermia induces autophagy by phosphorylating the Akt signaling pathway. Hypothermia has a more therapeutic effect when applied at the beginning of reperfusion rather than in the beginning of ischemia. Moderate hypothermia with 33°C poses most therapeutic effect by viability maintaining and reduction of reactive oxygen species release. Application of local hypothermia to myocardiocytes can be applied to infarcted myocardiocytes, anginal and to the cardiomyopathies.

An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice

BackgroundHypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment.MethodsPol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood–brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated.ResultsThis hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients.ConclusionOur study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.Graphical

Modern approach to the treatment of postoperative symptoms of patients undergoing oral surgery

Introduction. Removal of wisdom teeth is always accompanied by the appearance of collateral edema of varying severity, pain, neurological dysfunction and inflammatory contracture of the masticatory muscles.Purpose. To evaluate the use of local apparatus hypothermia and the method of three-dimensional facial scanning for the treatment of patients after extraction of mandibular third molars.Materials and methods. 60 patients had their wisdom teeth removed. Depending on the group, local apparatus hypothermia (LAH) (study group of 30 patients) and local ice hypothermia (LIH) (control group of 30 patients) were performed after surgery. Evaluation criterion: three-dimensional scanning of the face on days 3, 5, 7.Results. In the control group, on the 3rd day the size of the edema was 6.31 mm (SD 0.81), on the 5th day – 4.88 mm (SD 0.73), on the 7th day – 3.44 mm (SD 0.88). In the study group, on the 3rd day the size of the edema was 5.09 mm (SD 0.80), on the 5th day – 2.73 mm (SD 0.71), on the 7th day – 1.28 mm (SD 0,62). In the control group, the size of edema on the 5th day changed by 22.67% compared to the 3rd day, on the 7th day by 30.12% compared to the 5th day and by 45.94% compared to 3rd day. In the study group, the size of edema on the 5th day changed by 46.42% compared to the 3rd day, on the 7th day by 53.16% compared to the 5th day and by 75.32% compared 3rd day. Comparison of groups 3, 5 and 7 in terms of absolute values of edema size and percentage change showed a statistically significant difference (p&lt;0.001).Conclusion. The use of local apparatus hypothermia in the postoperative period can reduce the severity of collateral edema in a shorter period compared to standard methods of local hypothermia.

Aquarium fish and temperature neuropharmacology: Update

At the end of the 20th century in Russia, research on temperature dependence of specific pharmacological activity of antihypoxants and some neurotropic drugs under normo- and hypothermia of various biological objects in experimental and clinical conditions was started. At the beginning of the 21st century, an original biological model of acute hypoxia in aquarium fish was developed. This model made it possible to start the study of fish resistance to hypoxia, screen biologically active substances, and evaluate the activity of antihypoxants under normo- and hypothermia. The initial results of using this model allowed us to conclude that the dynamics of motor activity of fish under acute hypoxic conditions are similar to that of motor activity of fetuses inside the uterus under diagnostic intrauterine hypoxia created by voluntary apnea in a pregnant woman. The period of immobility of fish and fetuses under hypoxia was directly proportional to the value of their resistance to hypoxia. The reduction in conditions of acute hypoxic water temperature with floating fish in it at 10°C lengthens the duration of the immobile state of fish and preservation of their viability more than two times, and the preliminary introduction of hydrogen peroxide in the water in therapeutic dose along with hypothermia lengthens the corresponding periods by four times. Neurotropic drugs such as ethyl alcohol and local and general anesthetics will completely eliminate the pain syndrome that develops during local hypothermia in healthy patients. In addition, immersing the hands of people under alcohol intoxication and/or surgical anesthesia in water with melting ice for 2 min alleviates pain in the hands and accelerates the development of subsequent hyperemia in the skin of the hands by two times compared with the norm.

Motor Recovery after Spinal Cord Trauma and Effect of Local Hypothermia in a Porcine Experimental Model

Abstract This study was aimed to assess the therapeutic potential (expressed by improvement of pelvic extremities motor functions) of a 5-hour local application of hypothermia with cold saline (4 °C), or saline at room temperature (≈ 24 °C) conveyed via perfusion chamber placed epidurally over the epicenter of spinal cord lesion in minipigs paraplegic due to acute spinal cord injuries (SCIs) inflicted through L3 laminectomy with the force of 8N, 15N, or 18N by a computer operated contusion apparatus. Eighteen 5–8-month-old minipigs (Göttingen-Minnesota-Liběchov crossbreed strains weighing 28–35 kg) were randomly divided into 6 subgroups (each containing three animals) another 3 minipigs were added as sham controls. To evaluate the pelvic extremities motor recovery was used the porcine 20-point neurological scale. Regular evaluations of motor scores showed gradual spontaneous recovery of this parameter in all experimental animals, however, the best results achieved minipigs after SCI inflicted by 8N impacts. The data achieved in the study suggest that local application of therapeutic hypothermia (TH) is well tolerated and may improve functional outcomes after SCI. Further experimental and preclinical studies in different SCI animal models are required before the introduction of the method in healthcare practice.

Local Warm Alkaline Hydrogen Peroxide Solutions and Targeted Temperature Management Improve the Treatment of Chronic Wounds

Introduction: To date, there is no systematic review of the effect of local hypo-, normo- and hyperthermia on the processes of local interaction of antiseptics with dense biological masses covering the surface of chronic wounds. Accelerated and reliable cleansing of the wound surface from purulent masses still remains an unsolved problem of surgery. Methods: 6 inventions were found from beginning to 1986 in databases such as EAPATIS, BYPATENTS, DWPI, DEPATISnet, PATENTSCOPE, Espacenet, RUPTO, USPTO, CIPO, CNIPA, KIPRIS, PatSearch, J-PlatPat, Google Patents and TPO. Due to the small number of inventions, methodological heterogeneity, and differences in the content of their claims, a quantitative meta-analysis could not be performed. Results: The prospects of innovative proposals on the influence of local hypothermia and local hyperthermia on the process of local interaction of antiseptic drug solutions with purulent masses and blood on the surface of chronic wounds have been analyzed. The results of the included studies were presented only qualitatively (descriptively). Conclusion: The first review of inventions presents formulations of invented drugs created by physicochemical repurposing of hydrogen peroxide from antiseptic to pyolytics, mucolytics, hemolytics, expectorants and oxygen-releasing antihypoxants. Warm alkaline hydrogen peroxide solutions (WAHPSs) have been shown to rapidly and reliably dissolve thick purulent masses, blood clots and dried blood spots, turning them into a lush oxygenating foam. Temperature regimes that optimize the sanitizing and washing action of WAHPSs in the treatment of chronic wounds and accelerate hemostasis in parenchymatous bleeding are specified.

Targeted therapeutic hypothermia protects against noise induced hearing loss.

Exposure to occupational or recreational loud noise activates multiple biological regulatory circuits and damages the cochlea, causing permanent changes in hearing sensitivity. Currently, no effective clinical therapy is available for the treatment or mitigation of noise-induced hearing loss (NIHL). Here, we describe an application of localized and non-invasive therapeutic hypothermia and targeted temperature management of the inner ear to prevent NIHL. We developed a custom-designed cooling neck collar to reduce the temperature of the inner ear by 3-4°C post-injury to deliver mild therapeutic hypothermia. This localized and non-invasive therapeutic hypothermia successfully mitigated NIHL in rats. Our results show that mild hypothermia can be applied quickly and safely to the inner ear following noise exposure. We show that localized hypothermia after NIHL preserves residual hearing and rescues noise-induced synaptopathy over a period of months. This study establishes a minimally-invasive therapeutic paradigm with a high potential for rapid translation to the clinic for long-term preservation of hearing health.

Адамның басын салқындатуға арналған термоэлектрлік құрылғылары

The article analyzes the types of devices for cooling the human head and their effectiveness in medical practice. A brief description of the principle of operation of existing devices for hypothermia of the human brain is given, their advantages and disadvantages are described. Various methods of head cooling are considered, including the use of ice, water and air. The value of thermoelectric cooling devices for cooling the human head is determined. The need for further research in the field of creating optimal and safe technologies for cooling the human brain is shown. The results of the work can be used in the development of new methods of local hypothermia of the head.

Local apparatus hypothermia during surgical interventions in the oral cavity

Introduction. Dry ice cryotherapy is widely used in all areas of medicine, as this method can reduce swelling, hematoma. However, there are also disadvantages inherent in this method in the form of decompensation of the vascular bed, thereby going beyond the reserve forces of the body. Because of this, it is relevant to develop and apply the method of «soft» sequential cooling of the target area, for a more consistent spastic reaction of the vascular bed. In this clinical study, the technique of local hardware hypothermia was applied, which made it possible to reduce the likelihood of undesirable local decompensatory reactions from the body. Purpose. Clinical rationale for the use of local hardware hypothermia in the postoperative period in patients after complex extractions of 3 molars.Materials and methods. We studied 60 subjects diagnosed with retention and dystopia of the third molars of the n/h (30 control, 30 experimental groups). The experimental group after surgical interventions underwent PAH for 60 minutes with a target temperature of 18°C once, the control group received cryotherapy with an ice pack for 15 minutes (3 minutes exposure, 3 minutes rest 5 times). PAH was performed using the ViTherm apparatus (TsTKh Skolkovo, Moscow). The evaluation criteria in the study were: the type of wound healing, the presence of pain, swelling, lockjaw and discomfort, the use of NSAIDs, the presence of complications. The results of the study were entered into a table, with further statistical comparative analysis. For comparison, the Chi-square test with Yates correction was used. Results. In the control group, edema was observed in 100% of cases, and in the experimental group in 87%. Discomfort was felt by 87% and 83% of patients in the control and experimental groups, respectively. There were no complications in the experimental group, and 17% of patients in the control group (p=0.06). Pain was felt by 100% of patients in the control group and only 60% in the experimental group (p=0.0004). The intake of NSAIDs was 97% and 73%, respectively, in the control and experimental groups (p=0.03). In the experimental group, 73% of patients healed according to the primary type, and in 27% according to the secondary type. In the control group, primary healing occurs in 30% of cases, and secondary in 70% (p=0.002). In the control group, complications were observed in the form of alveolitis on the 3rd day after surgery (control n=5). 3 patients did not receive an injection of DMZ in the postoperative period at the request of the patient. In 31 patients the wound healed by primary intention (control n=9, experimental n=22), in 29 patients the wound healed by secondary intention (control n=20, experimental n=9), collateral edema was visually observed in 56 patients (control n=30 , experimental n=26). 48 patients complained of pain (control n=30, experimental n=18), discomfort when eating and talking, opening the mouth in 46 (control n=25, experimental n=21); 9 patients did not take NSAIDs (control n=1, experimental n=8). Conclusion. According to the statistical analysis and the results of the study, it can be said that the use of PAH in the postoperative period in patients after complex removal of 3 molars in the lower jaw reduces the likelihood of postoperative complications in the experimental group by 100%, pain by 40%, edema by 13%, the likelihood of secondary healing by 73%, trismus and discomfort by 17%, NSAIDs by 27% compared with the control group.

Method and technology for drug repurposing based on changes in the physicochemical properties of dosage forms: experience of use in Russia

Controlled local hyperthermia and hypothermia are important factors in drug pharmacodynamics and pharmacokinetics because changing the temperature of drugs changes their physicochemical properties. In this regard, a controlled change in the temperature of the drug and/or the body part with which the drug interacts, relative to the level of human body temperature (hyperthermia or hypothermia) forms the basis of temperature pharmacology. To analyze the authors publications on the problem of methodology and technology for repurposing drugs based on changes in the physicochemical properties of dosage forms. A controlled change in the temperature of the drug and/or the part of the body with which the drug interacts; a change in acid (alkaline), osmotic activity, and the degree and quality of carbonation and/or oxygen-forming activity of medicinal solutions; and a change in the concentration of medicinal solution ingredients. On the basis of the used methods, the reprofiling of a number of drugs has been achieved. The author proposed reprofiling a 4% potassium chloride solution from the group of macroelements and microelements used to regulate acid-base balance with a resorptive effect (when administered intravenously to the whole body) into a group of vasoconstrictive drugs used to stop bleeding when applied to by a single irrigation of the bleeding surface. Cooling certain drugs and tissues at their interaction sites to 18C20C (via an ice pack or its substitute) inhibits metabolism and function, ensuring the conversion of many drugs into anti-ischemic drugs by reducing the need for tissues in oxygen. A targeted change in the physicochemical properties of known drugs combined with local hyperthermia allows them to be converted into expectorant, pyrolytic (astringent), hemolytic, thrombolytic (hemostatic), detergent, bleaching, cleaning, and other drugs, including antiseptic and cauterizing (necrotizing) drugs, very reliably, quickly, and inexpensively. Thus, 40 years ago, pharmacologists of the Russian Federation established the foundation for a novel method of drug development known today as repurposing of existing drugs. Today, it is evident that reprofiling may rapidly, inexpensively, and effectively give existing drugs a new purpose.