Nitrous oxide (laughing gas balloons) - what is it and why is it dangerous?

Pharmacological properties

Pharmacodynamics

Dinitrogen oxide is a means for inhalation anesthesia. The mechanism of action is due to the ability to interact nonspecifically with neuronal membranes, inhibit the transmission of nerve impulses in the central nervous system, and change cortical-subcortical relationships.

Characterized by high analgesic activity. In small concentrations it causes mild drowsiness and a feeling of intoxication.

The analgesia stage is reached 2–3 minutes after inhalation of a gas mixture containing up to 80% nitrous oxide and 20% oxygen. 6–8 minutes after a short-term but quite pronounced stage of excitation, stage I of surgical anesthesia begins.

To maintain anesthesia, a dinitrogen oxide concentration of 40–50% with a corresponding increase in oxygen concentration is sufficient. In this case, sufficient relaxation of the skeletal muscles is not achieved. In this regard, to achieve the required effect, nitrous oxide is used in combination with other agents intended for inhalation anesthesia and muscle relaxants.

Awakening occurs 3–5 minutes after stopping the supply of the inhalation gas mixture.

Nitrous oxide depresses respiration, causes peripheral vasoconstriction, increases heart rate, and can increase intracranial pressure.

Pharmacokinetics

Through the lungs, nitrous oxide enters the systemic bloodstream. In plasma it is in a dissolved state and is not metabolized. It is excreted primarily through the lungs unchanged (after 10–15 minutes), in small quantities through the skin.

The half-life is 5–6 minutes.

Penetrates well through the blood-brain and placental barriers.

Indications for use

According to the instructions for use, nitrous oxide is used in the following cases:

• Inhalation combined anesthesia in combination with narcotic analgesics and muscle relaxants, carried out using special equipment;
• General anesthesia in operative gynecology, general surgery, dentistry and for pain relief during childbirth, which does not require muscle relaxation and deep anesthesia;
• Prevention of traumatic shock, as well as to enhance the analgesic and anesthetic effects of other drugs, including therapeutic analgesic anesthesia after surgery;
• Relief of pain in acute pancreatitis, myocardial infarction, acute coronary insufficiency;
• Switching off consciousness for pain relief during medical procedures.

A little history

The receipt of gas dates back to 1771. The preparation of this mixture of gases is attributed to the English chemist Joseph Presley. However, the properties of the gas were explored only in 1799. This was done, in the same England, by the chemist Humphry Davy.

It was he who first discovered that inhaling this gas leads to short-term intoxication, similar in its effects to intoxication. This is where the name “laughing gas” came from. The use of nitrous oxide for recreational purposes began practically from the discovery of these properties of the gas.

In our country, nitrous oxide has gained popularity relatively recently. Entertainment venues and nightclubs play a significant role in the spread, offering an inexpensive way to relax. It is actively sold on Internet resources. The reason for its popularity is its inexpensive price and availability.

In addition, distributors assure that the use of this gas is absolutely safe. Another factor that significantly increased the popularity of laughing gas was the ban on the over-the-counter sale of drugs containing codeine. It was nitrous oxide that replaced combination drugs containing codeine for drug addicts.

Contraindications

• Pathologies of the nervous system;
• Hypoxia;
• Chronic alcoholism or state of alcohol intoxication;
• Breastfeeding period;
• Hypersensitivity to the drug.

The drug should be used with caution in patients with traumatic brain injury, intracranial tumor, or a history of increased intracranial pressure.

If it is necessary to use it during pregnancy, the drug is prescribed in small concentrations (in a 1:1 ratio to oxygen) for a short time (within 2-3 breaths).

Nitrous oxide, instructions for use: method and dosage

Nitrous oxide is used in the form of inhalation in combination with oxygen and other anesthetics using special equipment for gas anesthesia in hospital settings.

Typically, anesthesia begins with a mixture containing 70-80% dinitrogen oxide and 20-30% oxygen.

Recommended concentration of dinitrogen oxide:

• Therapeutic anesthesia for the relief and prevention of pain: 40-75%;
• General anesthesia: dose for rapid immersion to the required depth of anesthesia - 70-75%, maintenance dose - 40-50%. If necessary, powerful narcotic drugs can be added to the mixture, including fluorotane, barbiturates, and ether. After turning off the supply of dinitrogen oxide, it is recommended to continue the oxygen supply for another 4-5 minutes in order to prevent diffusion hypoxia;
• Pain relief during labor: 40-75%, using the method of intermittent autoanalgesia, in which the woman in labor begins inhaling the mixture when warning signs of contraction appear and stops at its peak or towards the end of the contraction;
• Blackout for medical procedures: 25-50%.

The concentration of nitrous oxide for children is selected individually, and the oxygen content in the mixture should be 30% or more. After completion of anesthesia, it is necessary to continue inhalation oxygen supply for 5 minutes to prevent hypoxia.

Inhalation anesthesia is carried out against the background of premedication. In order to prevent nausea and vomiting, to reduce emotional arousal and enhance the effect, intramuscular administration of 2-3 ml of a 0.25% solution of droperidol (5-7.5 mg), 1-2 ml of a 0.5% solution of diazepam (5-10 mg).

Side effects

The use of Nitrous Oxide can cause side effects in the form of bradycardia, supraventricular arrhythmias, circulatory failure - during the period of introducing the patient into a state of general anesthesia.

Undesirable effects after recovery from anesthesia may include: drowsiness, nausea, vomiting, diffuse hypoxia, confusion, anxiety, agitation, nervousness, hallucinations, motor agitation. Long-term use (2 or more days) can lead to respiratory depression, impaired bone marrow function (leukopenia, pancytopenia), cause postoperative chills and hyperthermic crisis.

Disadvantages of this type of inhalation

Even this gentle inhalation method has its drawbacks. These include the following:

• It is impossible to put the patient into a state of deep anesthesia. This method does not allow for major surgery.
• If a large dose is administered, the level of oxygen saturation in the blood will decrease. This can cause hypoxia.
• The contractile activity of the myocardium will decrease slightly, but will decrease.
• If during the operation the patient feels severe pain, he may twitch sharply, thereby complicating the doctor’s work.
• Large doses may contribute to depression of brain activity.

Overdose

An overdose of Nitrous Oxide can be manifested by the following symptoms: respiratory depression, acute hypoxia, decreased blood pressure, arrhythmia, bradycardia, delirium.

Treatment:

• bradycardia: administration of atropine at a dose of 0.3–0.6 mg;
• arrhythmia: correction of gas levels in the blood;
• circulatory failure, arterial hypotension: reduction in the depth or cessation of general anesthesia, administration of plasma or plasma substitutes;
• hypertensive crisis: cessation of inhalation, increased oxygen supply, correction of metabolic acidosis and water-salt balance disorders, administration of antipyretics. If necessary, dantrolene is administered intravenously at a dose of 1 mg/kg (the total dose should not exceed 10 mg/kg) until the symptoms of the crisis stop. To avoid a relapse of the crisis, dantrolene is used for 1–3 days after surgery (orally or intravenously at a daily dose of 4–8 mg/kg in 4 divided doses);
• respiratory depression or inadequate postoperative ventilation: reducing the dose of anesthetic (if still used), maintaining the airway or artificial ventilation;
• delirium after recovery from general anesthesia: administration of a narcotic analgesic in small doses.

Medical Internet conferences

In 2001, a group of Saratov authors first proposed the use of millimeter-wave electromagnetic vibrations with frequencies corresponding to the rotational molecular spectra of the most important cellular metabolites (NO, CO, O2, CO2, OH, etc.) [1]. Since the molecular emission and absorption spectra of cellular metabolites are in the short-wave part of the submillimeter (terahertz) range [2], which is located on the scale of electromagnetic waves between the EHF and optical infrared ranges [3], the new direction is called “terahertz therapy” (THT therapy) [4].

It is known that metabolite molecules are the fundamental basis for the functioning of complex biological systems, so the possibility of controlling their reactivity, which can be used to regulate metabolic processes, is of extremely great interest.

To implement new scientific tasks, a panoramic spectrometric measuring complex with a quasi-optical reflectometer operating in the frequency range 118-600 GHz was created at JSC TsNIIIIA (Saratov) [1], since it is this range that includes the resonant absorption and emission spectra of the molecules of the above-mentioned cellular metabolites [2], including the molecular spectrum of emission and absorption of nitric oxide (150.176...150.644 GHz).

The molecular emission and absorption spectrum of nitric oxide (NO) attracted the attention of researchers first of all, since for more than 20 years the problem of nitric oxide has been one of the key ones in modern biology and medicine.

In 1987, the reaction of NO formation inside the cells of a macroorganism was discovered [5], after which methods for accelerating and slowing down this reaction, the interaction of NO with the nervous, endocrine and immune systems of the body, and the cytotoxicity of NO towards the macroorganism and microbes began to be intensively studied. The discovery of intracellular NO synthesis led to the discovery of a previously unknown regulatory system of the human and mammalian body – the nitric oxide system [5]. A new direction has emerged in biology—NO biology [6], which provides new fundamental information that can be used in medicine. A number of authors believe that the analysis of cyclic transformations of NO will be no less fruitful for physicians and biologists of the 21st century than the study of the tricarboxylic acid cycle in the mid-20th century [7].

In 1998, three American scientists - R. Furchgott, Luis J. Ignarro and F. Murad - were awarded the Nobel Prize in Physiology or Medicine for their discovery of the role of “nitric oxide” as a signaling molecule in the cardiovascular system" [8]. The nitric oxide molecule is called the “molecule of the 20th century” [7]. NO is not only a universal regulator of physiological and metabolic processes in an individual cell and in the body as a whole, but also carries out intercellular interactions, functioning as a signaling molecule in almost all organs and tissues of humans and animals [9-11]. A characteristic feature of NO is its ability to quickly diffuse through the membrane of the cell that synthesized it into the intercellular space and also easily (without the need for receptors) to penetrate target cells, which determines the properties of NO as a neurotransmitter [12, 13]. It was thanks to the study of nitric oxide that a new principle of signal transmission in biological systems was established: NO is formed in some cells, penetrates membranes and regulates the functions of other cells [7]. Endogenous NO is involved in many vital physiological processes. It is a universal modulator of various body functions, such as interneuronal communications, synaptic plasticity, the state of receptors, intracellular signal transmission, and the release of other neurotransmitters [13].

Inside the cell, NO activates some enzymes and inhibits others. The main physiological targets for NO are considered to be soluble guanylate cyclase and ADP-ribbosyltransferase [7, 14]. Activation of soluble guanylate cyclase causes an increase in cGMP, which in turn leads to a decrease in intracellular Ca2+ content [7]. According to many authors, the ability to regulate the intracellular concentration of Ca 2+ ions is one of the most important properties of NO [15].

Endogenous nitric oxide exists and is continuously synthesized in organs, tissues and cells enzymatically with the participation of NO synthases (NOS) - enzymes that use the amino acid L-arginine as the only substrate [6].

Three isoforms of NOS have been studied: endothelial, neuronal and macrophage [1,16]. Endothelial NOS is found in vascular endothelial cells, platelets, myocardium and endocardium. The endothelial mechanism for the formation of NO from L-arginine is activated during blood flow disturbances and under the influence of acetylcholine, bradykinin, histamine and platelet aggregation factor [1, 8, 16]. Neuronal NOS is found in neurocytes of the central nervous system and peripheral plexuses of the autonomic nervous system (ANS). There are nitrergic (nitrinergic) synapses in the CNS and ANS [1, 8]. Their mediator is NO. NO spreads along the efferent nitrergic nerves to the organs of the respiratory system, gastrointestinal tract, genitourinary system, and uterus [5, 16].

Neuronal and endothelial NOS have many common properties; they are combined together and called constitutive NOS [5, 16]. Constitutive NOS is calcium dependent because it requires Ca2+ for its activation. The enzyme synthesizes NO in physiological concentrations necessary to maintain body homeostasis; the steady-state level of NO maintained by constitutive NOS in tissues does not exceed several micromoles [16]. The formation of NO occurs in a discrete mode and in small portions, and only during those periods of time when the calcium concentration in the NO-synthesizing cell increases [5]. The hypothalamus–pituitary–adrenal cortex system does not have any inhibitory effect on constitutive NOS [5]. Constitutive NOS acts as an antagonist of the adrenergic nervous system in the regulation of blood pressure. Congenital or acquired deficiency of constitutive NOS leads to arterial hypertension, and its hyperfunction leads to hypotension.

In addition to constitutive NOS, “inducible” or “calcium-independent” NOS is also distinguished. It is found in macrophages (therefore it is also called “macrophage”), hepatocytes, fibroblasts, smooth muscle cells of blood vessels, the gastrointestinal tract and genitourinary system, muscle cells of the heart and uterus [5, 16-18]. Inducible NOS appears in cells only after their induction by bacterial toxins and certain inflammatory mediators, for example, proinflammatory cytokines [5, 16, 17]. In cells that are at rest, it is not detected. Inducible NOS synthesizes NO continuously, regardless of the calcium content in NO-synthesizing cells and in quantities hundreds of thousands of times higher than the NO concentrations produced by constitutive NOS [16]. Produced by inducible NOS NO is primarily intended to protect the host organism, helps reduce the activity of border inflammatory cells, the death of microorganisms and intracellular parasites, inhibiting platelet aggregation and improving local blood circulation [12].

The hypothalamus–pituitary–adrenal cortex system can prevent the activation of not yet activated inducible NOS, but cannot stop the secretion of NO that began under the influence of already activated inducible NOS [5]. It has been indirectly calculated that the rate of NO synthesis in a macroorganism can change millions of times [5].

Under hypoxic conditions, the stability of NO increases, which enhances its biological effect [7].

NO production can slow down or stop under the influence of ethanol, glucocorticosteroids, and indomethacin [7, 19].

NO is inactivated by blood hemoglobin with the formation of nitrosohemoglobin, which breaks down to methemoglobin [5]. Excess NO can bind when it interacts with superoxide radicals, thiols and metals (especially Fe2+) [20].

Nitric oxide has also been described as having undesirable effects. According to modern concepts, they are caused by the formation of the strongest oxidizing agent - peroxynitrite, which arises in the reaction of NO with the superoxide anion. Peroxynitrite acts as an integral link that unites two systems of active low-molecular agents that arise in cells and tissues - NO and reactive oxygen species [16].

High concentrations of NO have a cytotoxic or cytostatic effect on any cell, without differentiating whether it is a normal host cell, a tumor cell or a macrophage [5, 7]. The half-life of the NO molecule is measured in seconds, so its effect extends only to nearby cells [5]. It has been established that a chronic excess of NO in the body leads to autoimmune diseases [5].

It has been indirectly calculated that the rate of NO synthesis in a macroorganism can vary millions of times. Sharp hyperproduction of NO is a frequent accompaniment of severe acute therapeutic, surgical and infectious diseases [5]. At the same time, NO itself, excessively accumulating in the cell, can cause DNA damage and have a pro-inflammatory effect in endotoxemia, septic shock, and inflammatory lung diseases [12].

It should be especially emphasized that nowadays people are increasingly talking about the multifunctionality of the action of NO, which sometimes has the opposite character. Thus, it became known that NO can both enhance lipid peroxidation processes in cell membranes and inhibit them, cause both vasodilation and vasoconstriction, induce apoptotic cell death and have a protective effect against apoptosis induced by other agents [7, 21] . NO is characterized by both anticarcinogenic activity and mutagenic action [19].

The conditions under which the protective effect of NO becomes damaging are not clear enough. The multiple effects of NO can be explained by the presence of a large number of metabolic products in the nitric oxide cycle (NO2-, NO3-, NO+, NO-, NO2.-radical, etc.), which have different biological effects [7].

It is believed that the different effects of NO are determined by a variety of NO signaling pathways (which depend on the relative rate of NO formation, redox reactions, as well as combinations of oxygen, superoxide radical and other biological molecules) and the sensitivity of cellular systems to one or another signaling pathway [21 ]. The final effect of NO in blood vessels may depend on the site of its generation, local concentration, and interaction with other tissue components [20].

The biological effects of NO are of particular interest to cardiologists, since NO is a neurotransmitter, a powerful factor of hemostasis, an antiplatelet agent, an endogenous vasodilator [14, 16, 22-27], has a stress-limiting effect [28], and is directly involved in the mechanisms of modulation of the immune response [ 18], is a universal regulator of the central and peripheral nervous systems [7, 13]. Nitrinergic synapses have been described in the central nervous system and the autonomic nervous system, as well as nitrinergic nerves in the heart, gastrointestinal tract, respiratory tract and genitourinary system [5, 12], which suggests the existence of a third (along with choline and noradrenergic) type of nervous system [12] .

Nitric oxide, produced in the brain, is one of the most important levers by which the nervous system controls vascular tone, and several mechanisms of such regulation have been described - through direct stimulation of vasopressin release or by modulating the relationship in the hypothalamus-epiphysis-adrenal system [7].

However, the main mechanism of the vasodilatory effect of NO is directly related to the functioning of guanylate cyclase, and only its soluble form, and is mediated through the activation of soluble guanylate cyclase with the accumulation of cyclic 3', 5'-guanosine monophosphate (cGMP), which subsequently leads to the release of Ca2+ from muscle cells and into ultimately – to vasodilation [17]. It has been proven that NO is involved in the relaxation of vascular smooth muscles [7, 29, 30-34].

Moreover, it has been established that many physiological vasodilators exert their vasodilatory effect precisely through the activation of NO synthesis. The therapeutic effect of the most well-known nitrovasodilators - nitroglycerin, nitrosorbide, sodium nitroprusside, etc. - is also associated with the interaction of NO, formed as a result of their biotransformation, with the heme of guanylate cyclase, activation of the enzyme and accumulation of cGMP.

The known property of nitric oxide to inhibit platelet aggregation is also associated with its ability to activate soluble guanylate cyclase [14, 29, 35, 36]. Guanylate cyclase regulates aggregation through a feedback mechanism: initiation of aggregation promotes activation of the enzyme, and accumulating cGMP mediates a signal for disaggregation and inhibits aggregation through the general mechanism of inhibition of Ca2+ accumulation. Thus, guanylate cyclase can be considered as a protective mechanism against the development of aggregation. In this regard, targeted activation of guanylate cyclase by nitric oxide and NO-generating compounds can be used to attenuate the increased ability of platelets to aggregate. And since the regulatory role of guanylate cyclase manifests itself at the very early stages of the aggregation process, new enzyme activators will be able not only to weaken hyperaggregation, but also to prevent their spontaneous aggregation, and therefore, prevent the occurrence and development of vascular complications.

The cytoprotective effect of NO is due to its ability to prevent not only aggregation, but also platelet adhesion [16, 19].

It is known that nitric oxide helps normalize the functional state of the cell wall, as well as the coagulation potential of the blood and microcirculation [17, 34, 37].

In addition, under the influence of nitric oxide, there is a decrease in the aggregation ability of erythrocytes both in vitro and in vivo [38], a change in the geometry of blood vessels due to their dilatation [23, 27, 39], that is, endogenous nitric oxide largely determines the rheological properties blood, which primarily depend on the qualitative and quantitative composition of red blood cells.

Of great importance is the discovered anti-stress effect of NO, which is associated with its activation of stress-limiting mechanisms [28]. It is known that this reduces the content of fibrinogen in the blood, which affects both platelet aggregation and the rheological properties of blood [40-42].

With prolonged stress exposure, a decrease in the production of endogenous nitric oxide and a decrease in its regulatory functions occur [28].

It has been established that nitric oxide takes part in the regulation of lipid peroxidation: in physiological concentrations, NO acts as an antioxidant that inhibits the development of radical oxidative reactions by binding to free Fe2+ ions and heme ions and inhibiting the decomposition of peroxides [7].

Thus, the nitric oxide regulatory system influences the main pathogenetic mechanisms of the development of cardiovascular pathology: platelet hemostasis, hemocoagulation, rheological properties of blood, the functional state of the endothelial and smooth muscle components of the vascular wall, stress-limiting factors, lipid peroxidation.

Diseases of the cardiovascular system can develop both as a result of a decrease and as a result of an uncontrolled increase in the concentration of NO in the body.

A decrease in NO secretion leads to the development of arterial hypertension and pathology of the coronary vessels. Thus, the results of experiments on experimental animals revealed the existence of a causal relationship between a decrease in NO secretion and the occurrence of arterial hypertension [43, 44].

The mechanism of this action is explained, firstly, by the fact that NO is (along with prostacyclin, etc.) an activator of guanylate cyclase [17] and causes relaxation of vascular smooth muscles. Secondly, NO has blood pressure and central depressive effects, probably through its effect on the paraventricular nuclei of the hypothalamus and the nucleus of the solitary tract [17, 45]. It has been established that increased concentrations of endogenous NOS blockers are one of the causes of renal hypertension [46].

Studies with NO donors and inhibitors have shown that their intracoronary administration has a direct effect on the tone of the coronary arteries in patients with atherosclerosis or hypercholesterolemia. Thus, in patients with atherosclerosis of the coronary arteries, intracoronary infusion of the NO inhibitor acetylcholine leads to a paradoxical reaction - a decrease in the diameter of the subendocardial arteries, while in healthy people a similar procedure causes their increase [47]. Experiments with the NO donor L-arginine showed that its intracoronary administration in patients with hypercholesterolemia significantly increased coronary blood flow, which confirms the role of NO in the regulation of coronary tone [48]. It was noted that dysfunction of the vascular endothelium appears to manifest itself long before the development of clinically significant atherosclerosis [48].

Due to its vasodilatory properties and ability to inhibit the generation of O2-phagocytic cells, NO plays a key protective role in ischemic myocardial damage [7].

It is also known that nitric oxide, released in the sinoatrial node, is required to participate in the autonomic control of the heartbeat [7]. NO may also be involved in vascular remodeling processes [20].

The role of NO in the regulation of vascular tone of the lungs under hypoxic conditions has been proven: acute blockade of NO synthesis led to increased hypoxic vasoconstriction [12]. Insufficient formation and release of NO is the predominant mechanism for the development of pulmonary hypertension and the loss of the ability of pulmonary vessels to respond by vasodilation to endothelium-dependent substances during chronic hypoxia [12]. In many cases, NO inhalation eliminates pulmonary vasoconstriction associated with hypoxia, primary pulmonary hypertension, cardiac defects, and adult respiratory distress syndrome [12].

An increase in NO concentration is one of the pathogenetic links of various types of shocks [5]. It has been proven that a progressive decrease in blood pressure in cases of prolonged infectious-toxic shock is due to increased secretion of nitric oxide as a result of the expression of inducible NOS under the influence of inflammatory stimuli [20, 49]. In this case, there is refractoriness even to large doses of vasoconstrictors, but it has been proven that immediately after intravenous administration of NO inhibitors, blood pressure in such patients increases [49]. A similar situation is observed in hemorrhagic shock [50].

The concentration of NO in the blood increases not only in shock, but also in many other diseases [11, 51]. Most of them are characterized by a tendency to hypotension and a decrease in the reserve of contractile function of the heart.

The negative inotropic effect of proinflammatory cytokines on isolated papillary muscle is mediated by NO, which is an effective cytokine molecule [52]. The development of circulatory failure during systemic inflammatory reactions is also associated with hyperproduction of NO in blood vessels under the influence of inflammatory stimuli [20].

Inducible NOS was found in cardiomyocytes of patients with dilated cardiomyopathy, which is not found in healthy cardiomyocytes [53]. Experimental studies revealed a negative chronotropic effect of NO on the myocardium [54]. An increased level of NO in the blood is apparently one of the causes of impaired contractile function of the heart in dilated cardiomyopathy, myocarditis and myocardial infarction [55, 56].

It is known that local vascular reactions caused by atherosclerosis and endothelial destruction also lead to hyperproduction of nitric oxide as a result of the expression of inducible NOS [20].

The presented data indicate that both deficiency and excess of nitric oxide contribute to the emergence of a wide variety of pathologies of the cardiovascular system.

A decrease in NO secretion leads to the development of arterial hypertension, pathology of the coronary vessels, progression of prethrombotic and thrombotic conditions, impaired microcirculation, and increased hypoxic vasoconstriction of the pulmonary vessels. Nitric oxide plays a key protective role in ischemic myocardial damage, takes part in the pathogenesis of ischemic cerebral infarction, vascular remodeling processes, activation of stress-limiting factors, and in the mechanisms of modulation of the immune response.

An excessive increase in the concentration of NO in the blood leads to hypotension and a decrease in the reserve of contractile function of the heart, and is one of the pathogenetic links of various types of shocks.

Thus, for cardiologists, the issues of maintaining the physiological level of concentration and functional state of endogenous NO in the human body seem extremely relevant both scientifically and practically.

Of particular importance is the fact that the efficiency of the nitric oxide cycle increases sharply under functional loads associated with increased oxygen utilization, during cerebral and myocardial ischemia, and during numerous pathological processes occurring under hypoxic conditions. Only in cases where the use of oxygen is fully compensated by its supply can the role of the nitric oxide cycle remain the same as it performs under normal physiological conditions [57]. Consequently, the role of the nitric oxide cycle increases sharply in diseases such as coronary heart and brain disease, arterial hypertension, congenital and acquired heart defects, and myocardial dystrophy.

Currently, intensive searches are underway for methods to create pharmacological activators of guanylate cyclase based on chemical structures (donors) that provide the possibility of the formation of endogenous nitric oxide in the body, regulation of its concentration and reactivity [6, 14].

Unfortunately, drugs based on the described compounds have not yet been introduced into clinical practice. In addition, pharmacological correction of NO levels may be accompanied by undesirable side effects, since there are currently no available clinical methods for determining the concentration of nitric oxide in the bloodstream.

In connection with the above, it is of interest to use electromagnetic radiation in the millimeter range (EMR MW) or radiation in the extremely high frequency range (EHF radiation), which includes electromagnetic oscillations with a frequency from 3 ´ 1010 to 3 ´ 1011 Hz, as a potential regulator of the nitric oxide cycle. which corresponds to wavelengths from 1 to 10 mm [59]. One of the main properties of EMR MMD is the dependence of the results of exposure to EMR MMD on the phase of biological development and on the initial state of the object: EMR MMD has practically no effect on the normal functioning of a healthy organism [59, 60, 61], and if pathology occurs, it can regulate its functioning within limits inherent in a given biological species [62].

According to a number of modern authors, irradiation with terahertz EMR at frequencies of the molecular spectrum of nitric oxide (THN-NO EMR) can not only increase the synthesis of endogenous nitric oxide and increase its reactivity, but also increase the duration of existence of nitric oxide in cells [63].

Currently, a positive effect of EMR THC-NO on the functional properties of platelets and rheological parameters during irradiation of the blood of patients with angina pectoris in vitro has been revealed [64, 65], as well as the restoration of initially impaired rheological parameters and functional activity of platelets when irradiated with EMR THF-NO whites rats under immobilization stress [66].

Since 2004, after studying the effect of EMR at the frequencies of the molecular spectrum of nitric oxide in healthy volunteers, at the Department of FPC and PPS Therapy of Saratov Medical University, studies were first started to study the effect of TCG-NO therapy in cardiac patients [67]. The first results confirmed the supposed vasoactive, antianginal and hypocoagulative effects of THC-NO radiation [67], which allows us to consider THC-NO EMR as a new promising direction in the treatment of cardiovascular pathology, requiring serious study.

It was subsequently found that THC-NO therapy enhances the antianginal and hypotensive effects of drug treatment in patients with both stable and unstable angina, improves long-term treatment results for these categories of patients, and has a beneficial effect on the rheological properties of blood, which is extremely important for process optimization microcirculation, and also has a pronounced positive effect on the course of chronic DIC in patients with stable angina of high functional classes [68, 69].

At the same time, when studying the effect of EMR THC-NO in middle-aged and elderly patients with angina pectoris, results were obtained that indicate relatively independent dynamics of hemocoagulation potential indicators and the antianginal effect of THC therapy-NO [70]. Relief of angina attacks occurred equally in middle-aged and elderly patients, while changes in parameters of the thrombogenic potential of the blood varied significantly.

In middle-aged patients, the improvement in hemocoagulation parameters occurred due to an increase in the activity of the natural antithrombin-III anticoagulant until its complete normalization, while no effect on the procoagulant potential was noted. In the group of elderly patients, on the contrary, the effect of THC-NO therapy was realized through the positive dynamics of the level of natural procoagulants, and the effect was carried out on both the initial and final stages of blood coagulation, which was manifested in a decrease in the level of fibrinogen in combination with an extension of the AVR. At the same time, there was no dynamics of antithrombin-III activity [70]

Recent studies have established that the effectiveness of TCG-NO therapy depends on the severity of the initial condition of patients with angina pectoris III-IV. [71]

In patients with initially less frequent angina attacks (1-3 per day), in almost 90% (89.5%) it is possible to achieve complete disappearance of angina attacks by the time of discharge from the hospital. At the same time, the maximum antianginal effect of EMR THC-NO was revealed at the end of the course of treatment - at the 7th session.

In patients with angina pectoris III-IV f.k. with more frequent attacks (more than 3 per day), complete relief of angina attacks was achieved only in 51.4% of cases, which is significantly lower than in patients with milder angina, but the maximum antianginal effect was achieved earlier, by the 6th session [71]

Thus, in more severely ill patients, it is probably advisable to limit oneself to a shortened course of THC-NO therapy. The information obtained corresponds to one of the main provisions about the interaction of millimeter waves with living objects: with a more severe initial state, a less active effect is required to normalize homeostasis [59-62].

It is extremely interesting that the effect of THC-NO EMR on the parameters of hemocoagulation and blood rheology is fundamentally different in the two examined groups: with less frequent attacks of angina, only a decrease in the procoagulant potential was revealed, while in the group with more frequent painful attacks the activity of the anticoagulant increases and is restored. link, and also increases the deformability of erythrocytes [71]. It is not yet possible to explain the mechanism of such differences, taking into account the available information.

However, these results may be associated with the activation of various components of the nitric oxide cycle in certain groups of patients with angina, since it is known that the numerous, often opposite effects of nitric oxide are associated with a variety of NO signaling pathways (which depend on the relative rate of NO formation, redox reactions, as well as combinations of oxygen, superoxide radical and other biological molecules) and the sensitivity of cellular systems to one or another signaling pathway [12]. The final effect of NO may depend on the site of its generation, local concentration and interaction with other tissue components [11].

The results obtained indicate that THC-NO EMR is a promising method that influences the pathogenetic mechanisms of the development of cardiovascular pathology (thrombogenic potential, hemorheological parameters), increasing the antianginal and antihypertensive effects of medications.

At the same time, the identified differences in the effects of THC-NO therapy in individual groups of patients with angina pectoris require further research to develop an individual approach when using terahertz waves in clinical practice.

special instructions

The use of the drug must be accompanied by monitoring blood pressure, heart rate (HR), heart rhythm, as well as monitoring the state of gas exchange and respiration, and the patient’s body temperature. During anesthesia, it is recommended to periodically pump out gas from the endotracheal tube cuff.

The use of Nitrous Oxide is indicated in the treatment of infants and older children. The drug should not be prescribed to newborns.

Prolonged contact with the drug among medical personnel increases the risk of developing leukopenia.

Certain concentrations of the mixture with cyclopropane, ether, and chlorethyl are explosive.

For patients with chronic alcoholism, high concentrations of dinitrogen oxide are required.

Impact on the ability to drive vehicles and complex mechanisms

The drug is not used when driving vehicles and machinery.

Signs and symptoms of laughing gas addiction

You can suspect that a teenager is inhaling gas based on the following signs:

• causeless laughter;
• dizziness;
• fainting;
• frequent headaches.

Unfortunately, parents often miss the first bells, they are so barely noticeable. Long-term dependence on laughing gas is more difficult to hide; loved ones will easily suspect something is wrong based on the following symptoms:

• emotional instability;
• deep depression;
• insomnia;
• aggression;
• deterioration of hearing and touch;
• slurred speech;
• unsteady gait;
• chronic tonsillitis;
• bruises and abrasions all over the body.

Drug interactions

With simultaneous use of nitrous oxide:

• Amiodarone - increases the likelihood of arterial hypotension and bradycardia that cannot be controlled by atropine;
• Fentanyl and its derivatives - enhance the effect on the cardiovascular system, help reduce cardiac output and heart rate;
• Xanthines – increase the risk of arrhythmias;
• Tranquilizers, inhalation anesthesia agents, neuroleptics, narcotic analgesics, antihistamines - enhance the effect.

When combined, the drug enhances the effects of diazoxide, ganglion blockers, diuretics, coumarin and indandione derivatives, and agents that depress the nervous system and respiration.

Reviews of Nitrous Oxide

Reviews of nitrous oxide as a means for general anesthesia on websites and forums are few: anesthesia is well tolerated and does not cause serious side effects.

Most often there are reports of the use of nitrous oxide in dentistry in children. Parents write that nitrous oxide was recommended to them by a dentist as a sedative after the child flatly refused to have his teeth treated. In this case, the gas mixture is fed through the nose. The treatment, accompanied by sedation, was successful, the child was conscious, but calmer than usual. The only side effects described are drowsiness after the procedure.

The need for inhalations in pediatric dentistry

Most often, treatment with nitrous oxide is not carried out at the request of the parents. This method is chosen by the doctor when meeting the child. Nitrous oxide should be used for inhalation in the following situations:

• If the child has a lot of neglected teeth.
• With panic fear developing into hysteria. He will be afraid of the doctor and interfere with this treatment in every possible way. Sedation will calm the child and help him get rid of his fear of dentists.
• At preschool age. The baby simply will not be able to sit for an hour or more in the dentist's chair.

If the doctor insists on use, you must take his side. However, you should make sure that the child has no contraindications to this type of anesthesia.