Chronotropic and inotropic effect. Classification and mechanism of action of inotropic drugs Pharmacokinetics and dosing regimen

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Positive inotropic drugs affect preload and afterload correction. The main principle of their action is to increase the force of myocardial contraction. It is based on a universal mechanism associated with the effect on intracellular calcium.

The following requirements are put forward for drugs in this group:

• intravenous route of administration;
• the possibility of dose titration under the control of hemodynamic parameters;
• short half-life (for quick correction of side effects).

Classification

In modern cardiology, in the group of drugs with a positive inotropic mechanism of action, it is customary to distinguish two subgroups.

cardiac glycosides.

Non-glycoside inotropic drugs (stimulants):

• β1-adrenergic stimulants (norepinephrine, isoprenaline, dobutamine, dopamine);
• phosphodiesterase inhibitors;
• calcium sensitizers (levosimendan).

Mechanism of action and pharmacological effects

Stimulants of β1-adrenergic receptors. When β-adrenergic receptors are stimulated, G-proteins of the cell membrane are activated and a signal is transmitted to adenylate cyclase, which leads to the accumulation of cAMP in the cell, which stimulates the mobilization of Ca2+ from the sarcoplasmic reticulum. Mobilized Ca²+ leads to increased myocardial contraction. Derivatives of catecholamines have a similar effect. AT clinical practice prescribe dopamine (a natural precursor to the synthesis of catecholamines) and the synthetic drug dobutamine. The drugs of this group, administered intravenously, affect the following receptors:

• β1-adrenergic receptors (positive inotropic and chronotropic action);
• β2-adreioreceptors (bronchodilation, expansion of peripheral vessels);
• dopamine receptors (increased renal blood flow and filtration, dilatation of the mesenteric and coronary arteries).

Thus, the main effect of β1-adrenergic stimulants - a positive inotropic effect - is always combined with others. clinical manifestations which can have both positive and negative effects on clinical picture acute heart failure.

Phosphodiesterase inhibitors. In clinical practice, another mechanism for enhancing myocardial contractility is also used, based on a decrease in the breakdown of cAMP. Thus, the basis is to maintain a high level of cAMP in the cell, either by increasing synthesis (dobutamine) or by reducing decay. Reducing the breakdown of cAMP can be achieved by blocking the enzyme phosphodiesterase.

AT last years another effect of these drugs was discovered (in addition to the blockade of phosphodiesterase) - an increase in the synthesis of cGMP. An increase in the content of cGMP in the vessel wall leads to a decrease in its tone, that is, to a decrease in OPSS.

So, drugs of this subgroup, increasing myocardial contractility (due to blockade of cAMP destruction), also lead to a decrease in OPSS (due to cGMP synthesis), which allows you to simultaneously influence preload and afterload in acute heart failure.

calcium sensitizers. The classic representative of this subclass is levosimendan. The drug does not affect Ca²+ transport, but increases its affinity for troponin C. As is known, Ca²+ released from the sarcoplasmic reticulum destroys the troponin-tropomyosin complex that inhibits contraction and binds to troponin C, which stimulates myocardial contraction.

Arutyunov G.P.

Inotropic drugs

Heart - plentiful innervated organ. Among the sensitive formations of the heart, two populations of mechanoreceptors, concentrated mainly in the atria and left ventricle, are of primary importance: A-receptors respond to changes in the tension of the heart wall, and B-receptors are excited when it is passively stretched. Afferent fibers associated with these receptors are part of the vagus nerves. Free sensory nerve endings, located directly under the endocardium, are the terminals of afferent fibers that pass through the sympathetic nerves.

Efferent innervation of the heart carried out with the participation of both departments of the autonomic nervous system. The bodies of sympathetic preganglionic neurons involved in the innervation of the heart are located in gray matter lateral horns of the upper three thoracic segments of the spinal cord. Preganglionic fibers are sent to the neurons of the upper thoracic (stellate) sympathetic ganglion. Postganglionic fibers of these neurons along with parasympathetic fibers vagus nerve form the upper, middle and lower cardiac nerves. Sympathetic fibers permeate the entire organ and innervate not only the myocardium, but also elements of the conduction system.

The bodies of parasympathetic preganglionic neurons involved in innervation of the heart, located in medulla oblongata. Their axons are part of the vagus nerves. After the vagus nerve enters the chest cavity, branches depart from it, which are included in the composition of the cardiac nerves.

The processes of the vagus nerve, passing through the cardiac nerves, are parasympathetic preganglionic fibers. From them, excitation is transmitted to intramural neurons and then - mainly to the elements of the conduction system. The influences mediated by the right vagus nerve are addressed mainly to the cells of the sinoatrial node, and the left - to the cells of the atrioventricular node. The vagus nerves do not have a direct effect on the ventricles of the heart.

Innervating pacemaker tissue, autonomic nerves are able to change their excitability, thereby causing changes in the frequency of generation of action potentials and heart contractions ( chronotropic effect). Nervous influences change the rate of electrotonic transmission of excitation and, consequently, the duration of the phases of the cardiac cycle. Such effects are called dromotropic.

Since the action of mediators of the autonomic nervous system is to change the level of cyclic nucleotides and energy metabolism, autonomic nerves in general are able to influence the strength of heart contractions ( inotropic effect). Under laboratory conditions, the effect of changing the value of the excitation threshold of cardiomyocytes under the action of neurotransmitters was obtained, it is designated as bathmotropic.

Listed pathways of the nervous system on the contractile activity of the myocardium and the pumping function of the heart are, although extremely important, modulating influences secondary to myogenic mechanisms.

Training video of the innervation of the heart (nerves of the heart)

Adrenalin. This hormone is formed in the adrenal medulla and adrenergic nerve endings, is a direct-acting catecholamine, causes stimulation of several adrenergic receptors at once: a 1 -, beta 1 - and beta 2 - Stimulation a 1-adrenergic receptors is accompanied by a pronounced vasoconstrictor effect - a general systemic vasoconstriction, including precapillary vessels of the skin, mucous membranes, kidney vessels, as well as a pronounced narrowing of the veins. Stimulation of beta 1 -adrenergic receptors is accompanied by a distinct positive chronotropic and inotropic effect. Stimulation of beta 2 -adrenergic receptors causes bronchial dilatation.

Adrenalin often indispensable in critical situations, since it can restore spontaneous cardiac activity during asystole, increase blood pressure during shock, improve the automatism of the heart and myocardial contractility, increase heart rate. This drug stops bronchospasm and is often the drug of choice for anaphylactic shock. It is used mainly as a first aid and rarely for long-term therapy.

Solution preparation. Adrenaline hydrochloride is available as a 0.1% solution in 1 ml ampoules (diluted 1:1000 or 1 mg/ml). For intravenous infusion, 1 ml of a 0.1% solution of adrenaline hydrochloride is diluted in 250 ml of isotonic sodium chloride solution, which creates a concentration of 4 μg / ml.

Doses for intravenous administration:

1) in any form of cardiac arrest (asystole, VF, electromechanical dissociation), the initial dose is 1 ml of a 0.1% solution of adrenaline hydrochloride diluted in 10 ml of isotonic sodium chloride solution;

2) when anaphylactic shock and anaphylactic reactions - 3-5 ml of a 0.1% solution of adrenaline hydrochloride diluted in 10 ml of isotonic sodium chloride solution. Subsequent infusion at a rate of 2 to 4 mcg / min;

3) with persistent arterial hypotension, the initial rate of administration is 2 μg / min, if there is no effect, the rate is increased until the required level of blood pressure is reached;

4) action depending on the rate of administration:

Less than 1 mcg / min - vasoconstrictor,

From 1 to 4 mcg / min - cardiostimulating,

5 to 20 mcg/min - a- adrenostimulating,

More than 20 mcg / min - the predominant a-adrenergic stimulant.

Side effect: adrenaline can cause subendocardial ischemia and even myocardial infarction, arrhythmias and metabolic acidosis; small doses of the drug can lead to acute renal failure. In this regard, the drug is not widely used for long-term intravenous therapy.

Norepinephrine . Natural catecholamine, which is the precursor of adrenaline. It is synthesized in the postsynaptic endings of the sympathetic nerves and performs a neurotransmitter function. Norepinephrine stimulates a-, beta 1 -adrenergic receptors, almost no effect on beta 2 -adrenergic receptors. It differs from adrenaline in a stronger vasoconstrictor and pressor action, less stimulating effect on automatism and contractile ability of the myocardium. The drug causes a significant increase in peripheral vascular resistance, reduces blood flow in the intestines, kidneys and liver, causing severe renal and mesenteric vasoconstriction. The addition of small doses of dopamine (1 µg/kg/min) helps to preserve renal blood flow when norepinephrine is administered.

Indications for use: persistent and significant hypotension with a drop in blood pressure below 70 mm Hg, as well as a significant decrease in OPSS.

Solution preparation. The contents of 2 ampoules (4 mg of norepinephrine hydrotartrate are diluted in 500 ml of isotonic sodium chloride solution or 5% glucose solution, which creates a concentration of 16 μg / ml).

The initial rate of administration is 0.5-1 μg / min by titration until the effect is obtained. Doses of 1-2 mcg/min increase CO, more than 3 mcg/min - have a vasoconstrictor effect. With refractory shock, the dose can be increased to 8-30 mcg / min.

Side effect. With prolonged infusion, renal failure and other complications (gangrene of the extremities) associated with the vasoconstrictor effects of the drug may develop. With extravasal administration of the drug, necrosis may occur, which requires chipping the extravasate area with a solution of phentolamine.

dopamine . It is the precursor of norepinephrine. It stimulates a- and beta receptors, has a specific effect only on dopaminergic receptors. The effect of this drug is largely dependent on the dose.

Indications for use: acute heart failure, cardiogenic and septic shock; the initial (oliguric) stage of acute renal failure.

Solution preparation. Dopamine hydrochloride (dopamine) is available in 200 mg ampoules. 400 mg of the drug (2 ampoules) are diluted in 250 ml of isotonic sodium chloride solution or 5% glucose solution. In this solution, the concentration of dopamine is 1600 µg/ml.

Doses for intravenous administration: 1) the initial rate of administration is 1 μg / (kg-min), then it is increased until the desired effect is obtained;

2) small doses - 1-3 mcg / (kg-min) are administered intravenously; while dopamine acts mainly on the celiac and especially the renal region, causing vasodilation of these areas and contributing to an increase in renal and mesenteric blood flow; 3) with a gradual increase in speed to 10 μg/(kg-min), peripheral vasoconstriction and pulmonary occlusive pressure increase; 4) high doses - 5-15 mcg / (kg-min) stimulate beta 1-receptors of the myocardium, have an indirect effect due to the release of norepinephrine in the myocardium, i.e. have a distinct inotropic effect; 5) in doses above 20 mcg / (kg-min), dopamine can cause vasospasm of the kidneys and mesentery.

To determine the optimal hemodynamic effect, it is necessary to monitor hemodynamic parameters. If tachycardia occurs, it is recommended to reduce the dose or discontinue further administration. Do not mix the drug with sodium bicarbonate, as it is inactivated. Long-term use a- and beta-agonists reduces the effectiveness of beta-adrenergic regulation, the myocardium becomes less sensitive to the inotropic effects of catecholamines, up to the complete loss of the hemodynamic response.

Side effect: 1) increase in DZLK, the appearance of tachyarrhythmias is possible; 2) in high doses can cause severe vasoconstriction.

Dobutamine(dobutrex). It is a synthetic catecholamine that has a pronounced inotropic effect. Its main mechanism of action is stimulation. beta receptors and increased myocardial contractility. Unlike dopamine, dobutamine does not have a splanchnic vasodilating effect, but tends to systemic vasodilation. It increases heart rate and DZLK to a lesser extent. In this regard, dobutamine is indicated in the treatment of heart failure with low CO, high peripheral resistance against the background of normal or elevated blood pressure. When using dobutamine, like dopamine, ventricular arrhythmias are possible. An increase in heart rate by more than 10% of the initial level can cause an increase in the zone of myocardial ischemia. In patients with concomitant vascular lesions, ischemic necrosis of the fingers is possible. In many patients treated with dobutamine, there was an increase in systolic blood pressure by 10-20 mm Hg, and in some cases, hypotension.

Indications for use. Dobutamine is prescribed for acute and chronic heart failure caused by cardiac (acute myocardial infarction, cardiogenic shock) and non-cardiac causes (acute circulatory failure after injury, during and after surgery), especially in cases where the mean blood pressure is above 70 mm Hg. Art., and the pressure in the system of a small circle is above normal values. Assign with increased ventricular filling pressure and the risk of overloading the right heart, leading to pulmonary edema; with a reduced MOS due to the PEEP regimen during mechanical ventilation. During treatment with dobutamine, as with other catecholamines, careful monitoring of heart rate, heart rate, ECG, blood pressure and infusion rate is necessary. Hypovolaemia must be corrected before starting treatment.

Solution preparation. A vial of dobutamine containing 250 mg of the drug is diluted in 250 ml of 5% glucose solution to a concentration of 1 mg / ml. Saline dilution solutions are not recommended as SG ions may interfere with dissolution. Do not mix dobutamine solution with alkaline solutions.

Side effect. Patients with hypovolemia may experience tachycardia. According to P. Marino, ventricular arrhythmias are sometimes observed.

Contraindicated with hypertrophic cardiomyopathy. Due to its short half-life, dobutamine is administered continuously intravenously. The effect of the drug occurs in the period from 1 to 2 minutes. It usually takes no more than 10 minutes to create its stable plasma concentration and ensure the maximum effect. The use of a loading dose is not recommended.

Doses. The rate of intravenous administration of the drug, necessary to increase the stroke and minute volume of the heart, ranges from 2.5 to 10 μg / (kg-min). It is often necessary to increase the dose to 20 mcg / (kg-min), in more rare cases - more than 20 mcg / (kg-min). Dobutamine doses above 40 µg/(kg-min) may be toxic.

Dobutamine can be used in combination with dopamine to increase systemic BP in hypotension, increase renal blood flow and urine output, and prevent the risk of pulmonary congestion seen with dopamine alone. The short half-life of beta-adrenergic receptor stimulants, equal to several minutes, allows you to very quickly adapt the administered dose to the needs of hemodynamics.

Digoxin . Unlike beta-adrenergic agonists, digitalis glycosides have a long half-life (35 hours) and are eliminated by the kidneys. Therefore, they are less manageable and their use, especially in intensive care units, is associated with the risk of possible complications. If sinus rhythm is maintained, their use is contraindicated. With hypokalemia, renal failure against the background of hypoxia, manifestations of digitalis intoxication occur especially often. The inotropic effect of glycosides is due to the inhibition of Na-K-ATPase, which is associated with the stimulation of Ca 2+ metabolism. Digoxin is indicated for atrial fibrillation with VT and paroxysmal atrial fibrillation. For intravenous injections in adults, it is used at a dose of 0.25-0.5 mg (1-2 ml of a 0.025% solution). Introduce it slowly into 10 ml of 20% or 40% glucose solution. In emergency situations, 0.75-1.5 mg of digoxin is diluted in 250 ml of a 5% dextrose or glucose solution and administered intravenously over 2 hours. The required level of the drug in the blood serum is 1-2 ng / ml.

VASODILATORS

Nitrates are used as fast-acting vasodilators. The drugs of this group, causing the expansion of the lumen of the vessels, including the coronary ones, affect the state of pre- and afterload and during severe forms heart failure with high filling pressure significantly increase CO.

Nitroglycerine . The main action of nitroglycerin is the relaxation of vascular smooth muscles. In low doses, it provides a venodilating effect, in high doses it also dilates arterioles and small arteries, which causes a decrease in peripheral vascular resistance and blood pressure. Having a direct vasodilating effect, nitroglycerin improves the blood supply to the ischemic area of ​​the myocardium. The use of nitroglycerin in combination with dobutamine (10-20 mcg/(kg-min) is indicated in patients at high risk of myocardial ischemia.

Indications for use: angina pectoris, myocardial infarction, heart failure with an adequate level of blood pressure; pulmonary hypertension; high level of OPSS with elevated blood pressure.

Solution preparation: 50 mg of nitroglycerin is diluted in 500 ml of solvent to a concentration of 0.1 mg / ml. Doses are selected by titration.

Doses for intravenous administration. The initial dose is 10 mcg / min (low doses of nitroglycerin). Gradually increase the dose - every 5 minutes by 10 mcg / min (high doses of nitroglycerin) - until a clear effect on hemodynamics is obtained. The highest dose is up to 3 mcg / (kg-min). In case of overdose, hypotension and exacerbation of myocardial ischemia may develop. Intermittent administration therapy is often more effective than long-term administration. For intravenous infusions, systems made of polyvinyl chloride should not be used, since a significant part of the drug settles on their walls. Use systems made of plastic (polyethylene) or glass vials.

Side effect. Causes the conversion of part of hemoglobin into methemoglobin. An increase in the level of methemoglobin up to 10% leads to the development of cyanosis, and a higher level is life-threatening. To lower the high level of methemoglobin (up to 10%), a solution of methylene blue (2 mg / kg for 10 minutes) should be administered intravenously [Marino P., 1998].

With prolonged (from 24 to 48 hours) intravenous administration of a nitroglycerin solution, tachyphylaxis is possible, characterized by a decrease in therapeutic effect in cases of re-introduction.

After the use of nitroglycerin with pulmonary edema, hypoxemia occurs. The decrease in PaO 2 is associated with an increase in blood shunting in the lungs.

After using high doses of nitroglycerin, ethanol intoxication often develops. This is due to the use of ethyl alcohol as a solvent.

Contraindications: increased intracranial pressure, glaucoma, hypovolemia.

Sodium nitroprusside is a fast-acting balanced vasodilator that relaxes the smooth muscles of both veins and arterioles. It does not have a pronounced effect on heart rate and heart rate. Under the influence of the drug, OPSS and blood return to the heart are reduced. At the same time, coronary blood flow increases, CO increases, but myocardial oxygen demand decreases.

Indications for use. Nitroprusside is the drug of choice in patients with severe hypertension associated with low CO. Even a slight decrease in peripheral vascular resistance during myocardial ischemia with a decrease in the pumping function of the heart contributes to the normalization of CO. Nitroprusside has no direct effect on the heart muscle, it is one of the best drugs in the treatment of hypertensive crises. It is used for acute left ventricular failure without signs of arterial hypotension.

Solution preparation: 500 mg (10 ampoules) of sodium nitroprusside are diluted in 1000 ml of solvent (concentration 500 mg/l). Store in a place well protected from light. Freshly prepared solution has a brownish tint. The darkened solution is not suitable for use.

Doses for intravenous administration. The initial rate of administration is from 0.1 μg / (kg-min), with a low CO - 0.2 μg / (kg-min). At hypertensive crisis treatment begins with 2 mcg/(kg-min). The usual dose is 0.5 - 5 mcg / (kg-min). The average rate of administration is 0.7 µg/kg/min. The highest therapeutic dose is 2-3 mcg / kg / min for 72 hours.

Side effect. With prolonged use of the drug, cyanide intoxication is possible. This is due to the depletion of thiosulfite reserves in the body (in smokers, with malnutrition, vitamin B 12 deficiency), which is involved in the inactivation of cyanide formed during the metabolism of nitroprusside. In this case, the development of lactic acidosis, accompanied by headache, weakness and arterial hypotension, is possible. Intoxication with thiocyanate is also possible. Cyanides formed during the metabolism of nitroprusside in the body are converted to thiocyanate. The accumulation of the latter occurs in renal failure. The toxic concentration of thiocyanate in plasma is 100 mg/l.

What is a negative and positive inotropic effect? These are efferent pathways that go to the heart from the centers of the brain and together with them are the third level of regulation.

Discovery history

The effect that the vagus nerves have on the heart was first discovered by the brothers G. and E. Weber in 1845. They found that as a result of electrical stimulation of these nerves, there is a decrease in the strength and frequency of heart contractions, that is, an inotropic and chronotropic effect is observed. At the same time, the excitability of the heart muscle decreases (batmotropic negative effect) and, along with it, the speed with which excitation moves through the myocardium and the conduction system (dromotropic negative effect).

For the first time he showed how the irritation of the sympathetic nerve affects the heart, I.F. Zion in 1867, and then studied it in more detail by I.P. Pavlov in 1887. The sympathetic nerve affects the same areas of the heart as the vagus, but in the opposite direction. It manifests itself in a stronger contraction of the atrial ventricles, heart palpitations, increased cardiac excitability and faster conduction of excitation (positive inotropic effect, chronotropic, bathmotropic and dromotropic effects).

Innervation of the heart

The heart is an organ that is strongly innervated. An impressive number of receptors located in the walls of its chambers and in the epicardium give reason to consider it a reflexogenic zone. The most important in the field of sensitive formations of this organ are two types of mechanoreceptor populations, which are located mostly in the left ventricle and atria: A-receptors that respond to changes in the tension of the heart wall, and B-receptors that are excited during its passive stretching.

In turn, the afferent fibers associated with these receptors are among the vagus nerves. The free sensory endings of the nerves located under the endocardium are the terminals of the centripetal fibers that make up the sympathetic nerves. It is generally accepted that these structures are directly involved in the development of pain syndrome, radiating segmentally, which characterizes seizures. coronary disease. The inotropic effect is of interest to many.

Efferent innervation

Efferent innervation occurs due to both departments of the ANS. The sympathetic preanglionic neurons involved in it are located in the gray matter in the three upper thoracic segments in spinal cord, namely in the lateral horns. In turn, preanglionic fibers move to the neurons of the sympathetic ganglion (superior thoracic). The postganglionic fibers, together with the parasympathetic vagus nerve, create the upper, middle and lower nerves of the heart.

The entire organ is permeated by sympathetic fibers, while they innervate not only the myocardium, but also the components of the conduction system. The parasympathetic preanglionic neurons involved in the cardiac innervation of the body are located in the medulla oblongata. The axons related to them move among the vagus nerves. After the vagus nerve enters the chest cavity, branches that are included in the nerves of the heart depart from it.

The derivatives of the vagus nerve that run among the cardiac nerves are the parasympathetic preganglionic fibers. Excitation from them passes to intramural neurons, and then, first of all, to the components of the conducting system. The influences that are mediated by the right vagus nerve are mainly addressed by the cells of the sinoatrial node, and the left - by the atrioventricular node. The vagus nerves cannot directly affect the ventricles of the heart. The inotropic effect of cardiac glycosides is based on this.

intramural neurons

Located in the heart in large numbers as well as intramural neurons, and they can be located both singly and collected in the ganglion. The main number of these cells is located next to the sinoatrial and atrioventricular nodes, forming, together with efferent fibers located in the interatrial septum, the intracardiac plexus of nerves. It contains all the elements that are needed in order to close the local reflex arcs. It is for this reason that the intramural nervous cardiac apparatus is referred in some cases to the metasympathetic system. What else is interesting about the inotropic effect?

Features of the influence of nerves

At the time when the autonomic nerves innervate the tissue of pacemakers, they can affect their excitability and thus cause changes in the frequency of generation of action potentials and heartbeats (chronotropic effect). Also, the influence of nerves can change the rate of electrotonic transmission of excitation, and hence the duration of the phases of the heart cycle (dromotropic effects).

Since the action of mediators in the composition of the autonomic nervous system contains a change in energy metabolism and the level of cyclic nucleotides, in general, autonomic nerves can affect the strength of heart contractions, that is, an inotropic effect. Under the influence of neurotransmitters in laboratory conditions, the effect of changing the value of the excitation threshold of cardiomyocytes, which is designated as bathmotropic, was achieved.

All these ways through which nervous system effects on myocardial contractility and cardiac pumping are, of course, of exceptional importance, but are secondary to myogenic mechanisms that modulate influences. Where is the negative inotropic effect?

The vagus nerve and its influence

As a result of stimulation of the vagus nerve, a chronotropic negative effect appears, and against its background - a negative inotropic effect (drugs will be discussed below) and dromotropic. There are constant tonic influences of the bulbar nuclei on the heart: under the condition of its bilateral transection, the heart rate increases from one and a half to two and a half times. If the irritation is strong and prolonged, then the influence of the vagus nerves weakens over time or even stops. This is called the "escape effect" of the heart from the corresponding influence.

Isolation of the mediator

When the vagus nerve is stimulated, the chronotropic negative effect is associated with inhibition (or slowing down) of impulse generation in the driver heart rate sinus node. In the endings of the vagus nerve, when it is irritated, a mediator, acetylcholine, is released. Its interaction with muscarinic-sensitive cardiac receptors increases the permeability of the surface of the cell membrane of pacemakers for potassium ions. As a result, membrane hyperpolarization appears, slowing down or suppressing the development of slow spontaneous diastolic depolarization, as a result of which the membrane potential reaches a critical level later, which affects the slowing of the heart rate. With strong irritation of the vagus nerve, diastolic depolarization is suppressed, hyperpolarization of the pacemakers appears, and the heart stops completely.

During vagal influences, the amplitude and duration of atrial cardiomyocytes decreases. When the vagus nerve is stimulated, the atrial stimulation threshold rises, automation is suppressed, and the conduction of the atrioventricular node slows down.

Electrical stimulation of fibers

Electrical stimulation of the fibers that originate from the stellate ganglion results in an acceleration of the heart rate and an increase in myocardial contractions. In addition, the inotropic effect (positive) is associated with an increase in the permeability of the cardiomyocyte membrane for calcium ions. If the incoming calcium current increases, the level of electromechanical coupling expands, as a result of which there is an increase in myocardial contractility.

Inotropic drugs

Inotropic drugs are drugs that increase myocardial contractility. The most famous are cardiac glycosides ("Digoxin"). In addition, there are non-glycoside inotropic drugs. They are used only in acute heart failure or when there is severe decompensation in patients with chronic heart failure. The main non-glycoside inotropic drugs are: Dobutamine, Dopamine, Norepinephrine, Adrenaline. So, the inotropic effect in the activity of the heart is a change in the force with which it is reduced.

homeometric regulation

The force of contraction of the heart fiber can also change with changes in pressure (afterload). The rise in blood pressure increases the resistance to expulsion of blood and shortening of the heart muscle. As a result, one would expect a drop in VR. However, it has been repeatedly demonstrated that the SV remains constant over a wide range of resistances (the Anrep phenomenon).

In the increase in the force of contraction of the heart muscle with an increase in afterload, it was previously seen as a reflection of the "homeometric" self-regulation inherent in the heart, in contrast to the "heterometric" mechanism previously established by Starling. It was assumed that an increase in myocardial inotropy is involved in maintaining the value of SV. However, later it was found that the increase in resistance is accompanied by an increase in the end diastolic volume of the left ventricle, which is associated with a temporary increase in end-diastolic pressure, as well as myocardial extensibility associated with the influence of increased contraction force [Kapelko V.L. 1992]

In the context of sports activities, an increase in afterload is most often found during training aimed at developing strength and performing physical loads of a static nature. An increase in mean blood pressure during such exercises leads to an increase in the tension of the heart muscle, which, in turn, entails a pronounced increase in oxygen consumption, ATP resynthesis and activation of the synthesis of nucleic acids and proteins.

Inotropic effect of changes in heart rate

An important mechanism for the regulation of cardiac output is chronoinotropic dependence. There are two factors that affect the contractility of the heart in different directions: 1 - is aimed at reducing the strength of the subsequent contraction, is characterized by the rate of restoration of the ability to full contraction and is denoted by the term "mechanical restitution". Or mechanical restitution is the ability to restore the optimal force of a contraction after a previous contraction, which can be determined through the relationship between the duration interval R--R and the abbreviation that follows. 2 - increases the strength of the subsequent contraction with an increase in the previous contraction, denoted by the term "post-extrasystolic potentiation" and is determined through the relationship between the duration of the previous interval (R--R) and the strength of the subsequent contraction.

If the strength of contractions increases with an increase in the frequency of the rhythm, this is referred to as the Bowditch phenomenon (the positive effect of activation prevails over the negative one). If the strength of the contractions increases with the slowing of the rhythm frequency, then such a phenomenon is referred to as the "Woodworth's ladder". These phenomena are realized in a certain frequency range. When the frequency of contractions goes beyond the range, the force of contractions does not increase, but begins to fall.

The width of the range of these phenomena is determined by the state of the myocardium and the concentration of Ca 2+ in various cellular reserves.

AT experimental studies FZ Meyerson (1975) showed that in trained animals the inotropic effect of increasing heart rate is significantly higher than in control animals. This gives grounds to assert that under the influence of regular physical loads, the power of the mechanisms responsible for ion transport increases significantly. We are talking about an increase in the power of the mechanisms responsible for the removal of Ca 2+ from the sarcoplasm, i.e. calcium pump SPR and Na-Ca-exchange mechanism of the sarcolemma.

Opportunities for non-invasive study of the parameters of mechanical restitution and post-extrasystolic potentiation appeared among researchers due to the use of the method of transesophageal electrical stimulation in a stochastic mode. They performed electrical stimulation with a random sequence of impulses, registering synchronously the rheographic curve. On the basis of changes in the amplitude of the rewave and the duration of the period of exile, changes in myocardial contractility were judged. Later V.Fantyufiev et al. (1991) showed that such approaches can be successfully used not only in the clinic, but also in the functional diagnostic studies of athletes. Thanks to the study of the curves of mechanical restitution and post-extrasystolic potentiation in athletes, the authors were able to prove that these curves can significantly change with adaptation disorders to physical activity and overvoltage, and the introduction of magnesium ions or blockade of calcium current can significantly improve the contractility of the heart in some athletes. With an increase in heart rate, there is also an increase in the rate of the process of relaxation of the heart. This phenomenon was named by IT. Udelnov (1975) "rhythm-diastolic dependence". Later, F.Z. Meyerson and V.I. Kapelko (1978) proved that the rate of relaxation increases not only with an increase in frequency, but also with an increase in the amplitude or strength of contractions in the physiological range. They found that the relationship between contraction and relaxation is an important regularity in the activity of the heart and is the basis for a stable adaptation of the heart to stress.

In conclusion, it should be emphasized that regular sports training contributes to the improvement of cardiac regulation mechanisms, which ensures the economization of the work of the heart at rest and its maximum performance during extreme physical exertion.