Inotropic influence. Innervation of the heart
Drugs with inotropic effects include cardiac glycosides, β-adrenergic receptor agonists and phosphodiesterase inhibitors. Drugs of these groups increase the concentration of intracellular calcium, which is accompanied by increased myocardial contractility and an upward shift of the Frank-Starling curve (Fig. 9.10). As a consequence, at any end-diastolic volume (preload), stroke volume and CO increase. These drugs are indicated in the treatment of patients with systolic, but not diastolic, left ventricular dysfunction.
Rice. 9.10. Changes in the LV pressure-volume curve (Frank-Sterling curve) during therapy for heart failure. Point a corresponds to CH (the curve is shifted down). In HF, stroke volume is reduced (prior to the development of arterial hypotension) and LV end-diastolic pressure is increased, which is accompanied by symptoms of pulmonary congestion. Therapy with diuretics or drugs that have a venodilating effect (point b on the same curve) helps to reduce LV pressure without a significant change in stroke volume (SV). However, an excessive increase in diuresis or severe venodilation can lead to an undesirable decrease in VO and arterial hypotension (point b). While taking inotropic agents (point c) or vasodilators acting primarily on the arteriolar bed (as well as combined vasodilators) (point d), SV increases and LV end-diastolic pressure decreases (due to a more complete ejection of blood during systole). Point d reflects the possible positive effect of combination therapy with inotropic and vasodilator drugs. The dotted line shows an increase in the Frank-Starling curve during therapy with inotropic and vasodilator drugs (which, however, does not reach the level of functional activity of a normal LV)
In patients with a severe form of the disease receiving treatment in a hospital, $-adrenergic receptor agonists (dobutamine, dopamine) are sometimes administered intravenously to temporarily maintain hemodynamic parameters. Long-term use of these drugs is limited due to the lack of dosage forms for oral administration and rapidly developing tolerance - a progressive decrease in their therapeutic effectiveness due to a decrease in the number of adrenergic receptors in the myocardium according to the feedback principle. Phosphodiesterase inhibitors are usually used for severe heart failure of functional class III-IV, requiring intravenous therapy. Despite the high effectiveness of phosphodiesterase inhibitors at the beginning of treatment, the results of clinical studies indicate that therapy with these drugs does not significantly increase the life expectancy of patients.
In clinical practice, of all inotropic drugs, the most widely used are cardiac glycosides, which are prescribed both intravenously and orally. Cardiac glycosides enhance myocardial contractility, reduce LV dilatation, increase CO and help reduce the symptoms of HF. When taking cardiac glycosides, the sensitivity of baro-receptors increases, and, consequently, the sympathetic tone reflexively decreases, which leads to a decrease in afterload on the LV in patients with HF. In addition, cardiac glycosides help control heart rate, which has an additional positive effect in patients with concomitant atrial fibrillation. Therapy with cardiac glycosides reduces the symptoms of heart failure, but does not increase the life expectancy of patients in this category. Drugs of this class are not advisable for use in the treatment of patients with LV diastolic dysfunction, since they do not improve ventricular relaxation.
p-blockers
Previously, it was believed that β-blockers are contraindicated in LV systolic dysfunction, since their negative inotropic effect can lead to increased symptoms of the disease. However, the results of recent clinical studies indicate that therapy with β-blockers paradoxically helps to increase CO and normalize hemodynamic parameters. The mechanism of this phenomenon has not yet been studied, but it is believed that a decrease in heart rate, weakening of sympathetic tone and the anti-ischemic effect of beta-blockers may play a positive role in these cases. Currently, the use of β-blockers in the treatment of patients with HF remains the subject of clinical research.
Inotropic drugs are a group of drugs that increase the force of myocardial contraction.
CLASSIFICATION
Cardiac glycosides (see section “Cardiac glycosides”).
Non-glycoside inotropic drugs.
✧ Stimulants β 1-adrenergic receptors (dobutamine, dopamine).
✧
Phosphodiesterase inhibitors (amrinone℘ and milrinone ℘; they are not registered in the Russian Federation; allowed only for short courses for circulatory decompensation).
✧
Calcium sensitizers (levosimendan).
MECHANISM OF ACTION AND PHARMACOLOGICAL EFFECTS
Stimulantsβ
1
-adrenoreceptors
Drugs of this group, administered intravenously, affect the following receptors:
β 1- adrenoreceptors (positive inotropic and chronotropic effects);
β 2- adrenergic receptors (bronchodilation, peripheral vasodilation);
dopamine receptors (increased renal blood flow and filtration, dilatation of mesenteric and coronary arteries).
Positive inotropic effects are always combined with other clinical manifestations, which can have both positive and negative effects on the clinical picture of AHF. Dobutamine - selectiveβ 1is an adrenergic agonist, but it also has a weak effect onβ 2 - and α 1-adrenoreceptors. With the introduction of normal doses, an inotropic effect develops, sinceβ 1-stimulating effect on the myocardium predominates. A drug
Regardless of the dose, it does not stimulate dopamine receptors, therefore, renal blood flow increases only due to an increase in stroke volume.
Phosphodiesterase inhibitors.
Drugs of this subgroup, while increasing myocardial contractility, also lead to a decrease in peripheral vascular resistance, which makes it possible to simultaneously influence preload and afterload in AHF.
Calcium sensitizers.
A drug of this group (levosimendan) increases the affinity of Ca 2+
to troponin C, which enhances myocardial contraction. It also has a vasodilating effect (decreasing the tone of veins and arteries). Levosimendan has an active metabolite with a similar mechanism of action and a half-life of 80 hours, which causes a hemodynamic effect for 3 days after a single dose of the drug.
Clinical significance
Phosphodiesterase inhibitors may increase mortality.
In acute left ventricular failure secondary to acute myocardial infarction, the administration of levosimendan was accompanied by a reduction in mortality achieved in the first 2 weeks after the start of treatment, which persisted further (over 6 months of observation).
Levosimendan has advantages over dobutamine in terms ofstudy of the effect on blood circulation parameters in patients with severe decompensated CHF and low cardiac output.
INDICATIONS
Acute heart failure. Their purpose does not depend on the presence of venous stasis or pulmonary edema. There are several algorithms for prescribing inotropic drugs.
Shock due to an overdose of vasodilators, blood loss, dehydration.
Inotropic drugs should be prescribed strictly individually, it is necessary to evaluate central hemodynamic parameters, and also change the dose of inotropic drugs according to
with the clinical picture.
Dosing
Dobutamine.
The initial infusion rate is 2–3 mcg per 1 kg of body weight per minute. When administering dobutamine in combination with vasodilators, monitoring of pulmonary artery wedge pressure is necessary. If the patient received beta-adrenergic blockers, then the effect of dobutamine will develop only after the elimination of beta- adrenergic blocker.
Algorithm for the use of inotropic drugs (national recommendations).
Algorithm for the use of inotropic drugs (American Heart Association).
Dopamine.
The clinical effects of dopamine are dose dependent.
In low doses (2 mcg per 1 kg of body weight per minute or less when converted to lean body weight), the drug stimulates D 1 - and D 2-receptors, which is accompanied by dilation of the vessels of the mesentery and kidneys and allows to increase GFR in case of refractoriness to the action of diuretics.
In moderate doses (2–5 mcg per 1 kg of body weight per minute), the drug stimulatesβ 1- adrenoreceptors of the myocardium with an increase in cardiac output.
In high doses (5–10 mcg per 1 kg of body weight per minute), dopamine activatesα 1-adrenergic receptors, which leads to an increase in peripheral vascular resistance, left ventricular filling pressure, and tachycardia. Typically, high doses are prescribed in emergency situations to rapidly increase SBP.
Clinical features:
tachycardia is always more pronounced with the administration of dopamine compared to dobutamine;
dose calculations are carried out only for lean, and not for total body weight;
persistent tachycardia and/or arrhythmia that occurred during the administration of the “renal dose” indicate that the rate of drug administration was too high.
Levosimendan.
Administration of the drug begins with a loading dose (12–24 mcg per 1 kg of body weight for 10 minutes), and then proceeds to a long-term infusion (0.05–0.1 mcg per 1 kg of body weight). The increase in stroke volume and decrease in pulmonary artery wedge pressure are dose-dependent. In some cases it is possibleincreasing the dose of the drug to 0.2 mcg per 1 kg of body weight. The drug is effective only in the absence of hypovolemia. Levosimendan is compatible withβ
-adrenergic blockers and does not lead to an increase in the number of rhythm disturbances.
Features of prescribing inotropic drugs to patients with decompensated chronic heart failure
Due to the pronounced adverse effect on the prognosis, non-glycoside inotropic drugs can be prescribed only in short courses (up to 10–14 days) with a clinical picture of persistent arterial hypotension in patients with severe decompensation of CHF and a reflex kidney.
SIDE EFFECTS
Tachycardia.
Supraventricular and ventricular rhythm disturbances.
Subsequent increase in left ventricular dysfunction (due to increased energy consumption to ensure increased myocardial work).
Nausea and vomiting (dopamine in high doses).
Inotropic drugs- These are drugs that increase myocardial contractility. The most well-known inotropic drugs include cardiac glycosides. At the beginning of the 20th century, almost all cardiology was based on cardiac glycosides. And even in the early 80s. glycosides remained the main drugs in cardiology.
The mechanism of action of cardiac glycosides is blockade of the sodium-potassium “pump”. As a result, the supply of sodium ions into the cells increases, the exchange of sodium ions for calcium ions increases, this, in turn, causes an increase in the content of calcium ions in the myocardial cells and a positive inotropic effect. In addition, glycosides slow down AV conduction and reduce heart rate (especially with atrial fibrillation) - due to vagomimetic and antiadrenergic effects.
The effectiveness of glycosides for circulatory failure in patients without atrial fibrillation was not very high and was even questioned. However, special studies have shown that glycosides have a positive inotropic effect and are clinically effective in patients with impaired left ventricular systolic function. Predictors of the effectiveness of glycosides are: an increase in heart size, a decrease in ejection fraction and the presence of a third heart sound. In patients without these signs, the likelihood of the effect of prescribing glycosides is low. Currently, digitalization is no longer applied. As it turned out, the main effect of glycosides is the neurovegetative effect, which manifests itself when small doses are prescribed.
Nowadays, the indications for the use of cardiac glycosides are clearly defined. Glycosides are indicated in the treatment of severe chronic heart failure, especially if the patient has atrial fibrillation. And not just atrial fibrillation, but a tachysystolic form of atrial fibrillation. In this case, glycosides are the first choice drugs. The main cardiac glycoside is digoxin. Other cardiac glycosides are currently almost never used. For the tachysystolic form of atrial fibrillation, digoxin is prescribed under control of the ventricular rate: the target is a heart rate of about 70 per minute. If, while taking 1.5 tablets of digoxin (0.375 mg), it is not possible to reduce the heart rate to 70 per minute, P-blockers or amiodarone are added. In patients with sinus rhythm, digoxin is prescribed if there is severe heart failure (stage II B or III-IV FC) and the effect of taking an ACE inhibitor and diuretic is insufficient. In patients with sinus rhythm and heart failure, digoxin is prescribed at a dose of 1 tablet (0.25 mg) per day. In this case, for elderly people or patients who have had a myocardial infarction, as a rule, half or even a quarter of a digoxin tablet (0.125-0.0625 mg) per day is enough. Intravenous glycosides are prescribed extremely rarely: only for acute heart failure or decompensation of chronic heart failure in patients with a tachysystolic form of atrial fibrillation.
Even in such doses: from 1/4 to 1 tablet of digoxin per day, cardiac glycosides can improve the well-being and condition of severe patients with severe heart failure. Increased mortality in patients with heart failure has been observed with higher doses of digoxin. In mild heart failure (stage II A), glycosides are useless.
The criteria for the effectiveness of glycosides are improved well-being, a decrease in heart rate (especially with atrial fibrillation), an increase in diuresis, and an increase in performance.
The main signs of intoxication: the occurrence of arrhythmias, loss of appetite, nausea, vomiting, weight loss. When small doses of glycosides are used, intoxication develops extremely rarely, mainly when digoxin is combined with amiodarone or verapamil, which increase the concentration of digoxin in the blood. If intoxication is detected in a timely manner, temporary withdrawal of the drug followed by dose reduction is usually sufficient. If necessary, additionally use potassium chloride 2% -200.0 and/or magnesium sulfate 25% -10.0 (if there is no AV block), for tachyarrhythmias - lidocaine, for bradyarrhythmias - atropine.
In addition to cardiac glycosides, there are non-glycoside inotropic drugs. These drugs are used only in cases of acute heart failure or in severe decompensation of patients with chronic heart failure. The main non-glycoside inotropic drugs include: dopamine, dobutamine, epinephrine and norepinephrine. These drugs are administered only intravenously by drip in order to stabilize the patient’s condition and bring him out of decompensation. After this, they switch to taking other medications.
The main groups of non-glycoside inotropic drugs:
1. Catecholamines and their derivatives: adrenaline, norepinephrine, dopamine.
2. Synthetic sympathomimetics: dobutamine, isoproterenol.
3. Phosphodiesterase inhibitors: amrinone, milrinone, enoxymone (drugs such as imiobendan or vesnarinone, in addition to inhibiting phosphodiesterase, directly affect sodium and/or calcium current through the membrane).
Table 8
Non-glycoside inotropic drugs
|
A drug |
Initial infusion rate, mcg/min |
Approximate maximum infusion rate |
|
Adrenalin |
10 µg/min |
|
|
Norepinephrine |
15 µg/min |
|
|
Dobutamine |
||
|
Isoproterenol |
||
|
700 µg/min |
||
|
Vasopressin |
Norepinephrine. Stimulation of 1- and α-receptors causes increased contractility and vasoconstriction (but the coronary and cerebral arteries dilate). Reflex bradycardia is often observed.
Dopamine. A precursor to norepinephrine and promotes the release of norepinephrine from nerve endings. Dopamine receptors are located in the vessels of the kidneys, mesentery, coronary and cerebral arteries. Their stimulation causes vasodilation in vital organs. When infused at rates up to approximately 200 mcg/min (up to 3 mcg/kg/min), vasodilation is achieved (“renal” dose). When the dopamine infusion rate increases above 750 mcg/min, the stimulation of α-receptors and the vasoconstrictor effect (“pressor” dose) begin to predominate. Therefore, it is rational to administer dopamine at a relatively low rate - approximately in the range from 200 to 700 mcg/min. If a higher rate of dopamine administration is necessary, they try to connect an infusion of dobutamine or switch to an infusion of norepinephrine.
Dobutamine. Selective stimulator of 1-receptors (however, slight stimulation of 2- and α-receptors is also noted). When dobutamine is administered, a positive inotropic effect and moderate vasodilation are observed.
For refractory heart failure, dobutamine infusion is used for a duration of several hours to 3 days (tolerance usually develops by the end of 3 days). The positive effect of periodic infusion of dobutamine in patients with severe heart failure can last quite a long time - up to 1 month or more.
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 are 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 constriction of the veins. Stimulation of beta 1-adrenergic receptors is accompanied by a clear positive chronotropic and inotropic effect. Stimulation of beta 2 adrenergic receptors causes dilatation of the bronchi.
Adrenalin often indispensable in critical situations, since it can restore spontaneous cardiac activity during asystole, increase blood pressure during shock, improve the automaticity of the heart and myocardial contractility, and increase heart rate. This drug relieves bronchospasm and is often the drug of choice for anaphylactic shock. Used mainly as a first aid remedy and rarely for long-term therapy.
Preparation of the solution. Adrenaline hydrochloride is available in the form of a 0.1% solution in 1 ml ampoules (at a dilution of 1:1000 or 1 mg/ml). For intravenous infusion, 1 ml of 0.1% adrenaline hydrochloride solution is diluted in 250 ml of isotonic sodium chloride solution, which creates a concentration of 4 mcg/ml.
1) for 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) for 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) in case of persistent arterial hypotension, the initial rate of administration is 2 mcg/min, if there is no effect, the rate is increased until the required blood pressure level is achieved;
4) action depending on the rate of administration:
Less than 1 mcg/min - vasoconstrictor,
From 1 to 4 mcg/min - cardiac stimulant,
From 5 to 20 mcg/min - A-adrenergic stimulant
More than 20 mcg/min is the predominant α-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 . A natural catecholamine that is a precursor to adrenaline. It is synthesized in the postsynaptic endings of sympathetic nerves and performs a neurotransmitter function. Norepinephrine stimulates A-, beta 1-adrenergic receptors, has almost no effect on beta 2-adrenergic receptors. It differs from adrenaline in having a stronger vasoconstrictor and pressor effect, and a lesser stimulating effect on the 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 low doses of dopamine (1 mcg/kg/min) helps preserve renal blood flow during the administration of norepinephrine.
Indications for use: persistent and significant hypotension with a drop in blood pressure below 70 mm Hg, as well as with a significant decrease in peripheral vascular resistance.
Preparation of the solution. Contents of 2 ampoules (4 mg of norepinephrine hydrotartrate is 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 mcg/min by titration until the effect is achieved. Doses of 1-2 mcg/min increase CO, over 3 mcg/min have a vasoconstrictor effect. For 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 effect of the drug may develop. With extravasal administration of the drug, necrosis may occur, which requires injecting the extravasate area with a phentolamine solution.
Dopamine . It is a precursor to norepinephrine. It stimulates A- and beta receptors, has a specific effect only on dopaminergic receptors. The effect of this drug largely depends on the dose.
Indications for use: acute heart failure, cardiogenic and septic shock; initial (oliguric) stage of acute renal failure.
Preparation of the solution. Dopamine hydrochloride (dopamine) is available in ampoules of 200 mg. 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 mcg/ml.
Doses for intravenous administration: 1) the initial rate of administration is 1 mcg/(kg-min), then it is increased until the desired effect is obtained;
2) small doses - 1-3 mcg/(kg-min) administered intravenously; in this case, dopamine acts predominantly 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) large 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, monitoring of hemodynamic parameters is necessary. If tachycardia occurs, it is recommended to reduce doses or discontinue further administration. Do not mix the drug with sodium bicarbonate, as it is inactivated. Long-term use A- and beta-agonists reduce 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) increased PCWP, possible appearance of tachyarrhythmias; 2) in large doses it can cause severe vasoconstriction.
Dobutamine(dobutrex). This is a synthetic catecholamine that has a pronounced inotropic effect. The main mechanism of its action is stimulation beta-receptors and increased myocardial contractility. Unlike dopamine, dobutamine does not have a splanchnic vasodilating effect, but has a tendency to systemic vasodilation. It increases heart rate and PCWP 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% from the initial level can cause an increase in the area of myocardial ischemia. In patients with concomitant vascular lesions, ischemic necrosis of the fingers is possible. Many patients receiving dobutamine experienced an increase in systolic blood pressure by 10-20 mmHg, 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 average blood pressure is above 70 mm Hg. Art., and the pressure in the small circle system is higher than normal values. Prescribed for increased ventricular filling pressure and the risk of overload of the right heart, leading to pulmonary edema; with reduced MOS caused by the PEEP mode during mechanical ventilation. During treatment with dobutamine, as with other catecholamines, careful monitoring of heart rate, heart rhythm, ECG, blood pressure and infusion rate is necessary. Hypovolemia must be corrected before starting treatment.
Preparation of the solution. A bottle 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 solutions are not recommended for dilution because SG ions may interfere with dissolution. Dobutamine solution should not be mixed with alkaline solutions.
Side effect. In patients with hypovolemia, tachycardia is possible. 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 a period of 1 to 2 minutes. To create its stable concentration in plasma and ensure maximum action, it usually takes no more than 10 minutes. The use of a loading dose is not recommended.
Doses. The rate of intravenous administration of the drug required to increase the stroke and cardiac output ranges from 2.5 to 10 mcg/(kg-min). Often a dose increase to 20 mcg/(kg-min) is required, in more rare cases - over 20 mcg/(kg-min). Doses of dobutamine above 40 mcg/(kg-min) may be toxic.
Dobutamine can be used in combination with dopamine to increase systemic blood pressure during hypotension, increase renal blood flow and urine output, and prevent the risk of pulmonary circulatory overload observed with dopamine alone. The short half-life of beta-adrenergic receptor stimulants, equal to several minutes, allows the administered dose to be very quickly adapted to hemodynamic needs.
Digoxin . Unlike beta-adrenergic agonists, digitalis glycosides have a long half-life (35 hours) and are eliminated by the kidneys. Therefore, they are less controllable 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. In case of hypokalemia, renal failure against the background of hypoxia, manifestations of digitalis intoxication occur especially often. The inotropic effect of glycosides is due to inhibition of Na-K-ATPase, which is associated with stimulation of Ca 2+ metabolism. Digoxin is indicated for atrial fibrillation with VT and paroxysmal atrial fibrillation. For intravenous injections in adults, use a dose of 0.25-0.5 mg (1-2 ml of 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. Drugs of this group, causing expansion of the lumen of blood vessels, including coronary ones, affect the state of pre- and afterload and, in severe forms of heart failure with high filling pressure, significantly increase CO.
Nitroglycerine . The main effect of nitroglycerin is to relax the smooth muscles of blood vessels. 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. By having a direct vasodilating effect, nitroglycerin improves 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 developing myocardial ischemia.
Indications for use: angina pectoris, myocardial infarction, heart failure with adequate blood pressure levels; pulmonary hypertension; high level of peripheral vascular resistance with elevated blood pressure.
Preparation of the solution: 50 mg of nitroglycerin is diluted in 500 ml of solvent to a concentration of 0.1 mg/ml. Doses are selected by titration method.
Doses for intravenous administration. The initial dose is 10 mcg/min (low doses of nitroglycerin). The dose is gradually increased - 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. Therapy with intermittent administration 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 bottles.
Side effect. Causes the conversion of part of hemoglobin into methemoglobin. An increase in methemoglobin levels up to 10% leads to the development of cyanosis, and higher levels are life-threatening. To reduce high levels of methemoglobin (up to 10%), a solution of methylene blue (2 mg/kg for 10 minutes) should be administered intravenously [Marino P., 1998].
With long-term (24 to 48 hours) intravenous administration of nitroglycerin solution, tachyphylaxis is possible, characterized by a decrease in the therapeutic effect in cases of repeated administration.
After using nitroglycerin for pulmonary edema, hypoxemia occurs. A 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- a fast-acting, balanced vasodilator that relaxes the smooth muscles of both veins and arterioles. Does not have a pronounced effect on heart rate and heart rhythm. Under the influence of the drug, peripheral vascular resistance and blood return to the heart are reduced. At the same time, coronary blood flow increases, CO increases, but the myocardial oxygen demand decreases.
Indications for use. Nitroprusside is the drug of choice in patients with severe hypertension and 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 and is one of the best drugs for the treatment of hypertensive crises. It is used for acute left ventricular failure without signs of arterial hypotension.
Preparation of the solution: 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. The freshly prepared solution has a brownish tint. A darkened solution is not suitable for use.
Doses for intravenous administration. The initial rate of administration is from 0.1 mcg/(kg-min), with low DC - 0.2 mcg/(kg-min). In case of 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 mcg/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 eating disorders, vitamin B12 deficiency), which takes part in the inactivation of cyanide formed during the metabolism of nitroprusside. In this case, the development of lactic acidosis is possible, accompanied by headache, weakness and arterial hypotension. Thiocyanate intoxication 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.
Table of contents of the topic "Excitability of the cardiac muscle. Cardiac cycle and its phase structure. Heart sounds. Innervation of the heart.":1. Excitability of the heart muscle. Myocardial action potential. Myocardial contraction.
2. Excitation of the myocardium. Myocardial contraction. Coupling of excitation and contraction of the myocardium.
3. Cardiac cycle and its phase structure. Systole. Diastole. Asynchronous contraction phase. Isometric contraction phase.
4. Diastolic period of the ventricles of the heart. Relaxation period. Filling period. Cardiac preload. Frank-Starling law.
5. Activity of the heart. Cardiogram. Mechanocardiogram. Electrocardiogram (ECG). ECG electrodes
6. Heart sounds. First (systolic) heart sound. Second (diastolic) heart sound. Phonocardiogram.
7. Sphygmography. Phlebography. Anacrota. Catacrota. Phlebogram.
8. Cardiac output. Regulation of the cardiac cycle. Myogenic mechanisms of regulation of cardiac activity. Frank-Starling effect.
10. Parasympathetic effects on the heart. Influence of the vagus nerve on the heart. Vagal effects on the heart.
Heart - abundantly 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 passing through the sympathetic nerves.
Efferent innervation of the heart carried out with the participation of both parts of the autonomic nervous system. The bodies of sympathetic preganglionic neurons involved in the innervation of the heart are located in the gray matter of the lateral horns of the three upper thoracic segments of the spinal cord. Preganglionic fibers are directed to the neurons of the superior thoracic (stellate) sympathetic ganglion. The postganglionic fibers of these neurons, together with the parasympathetic fibers of the vagus nerve, form the upper, middle and lower cardiac nerves. Sympathetic fibers penetrate the entire organ and innervate not only the myocardium, but also elements of the conduction system.
Cell bodies of parasympathetic preganglionic neurons involved in innervation of the heart, are located in the medulla oblongata. Their axons are part of the vagus nerves. After the vagus nerve enters the chest cavity, branches branch off from it and become part of the cardiac nerves.
The processes of the vagus nerve, passing as part of the cardiac nerves, are parasympathetic preganglionic fibers. From them, excitation is transmitted to intramural neurons and further - 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). In laboratory conditions, the effect of changing the threshold value of cardiomyocyte excitation under the influence of neurotransmitters was obtained; it is designated as bathmotropic.
Listed pathways affecting 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.
