inotropic effect. Innervation of the heart
Inotropic drugs include cardiac glycosides, $-adrenergic agonists, and phosphodiesterase inhibitors. The drugs of these groups increase the concentration of intracellular calcium, which is accompanied by an increase in myocardial contractility and an upward shift in the Frank-Starling curve (Fig. 9.10). As a consequence, with any end-diastolic volume (preload), stroke volume and CO increase. These drugs are indicated in the treatment of patients with systolic but not diastolic LV dysfunction.
Rice. 9.10. Change in the curve of pressure - LV volume (Frank-Sterling curve) during the treatment of heart failure. Point a corresponds to CH (the curve is shifted down). In HF, the stroke volume is reduced (before the development of arterial hypotension) and the LV end-diastolic pressure is increased, which is accompanied by symptoms of congestion in the lungs. Therapy with diuretics or drugs that have a venodilatory effect (point b on the same curve) helps to reduce pressure in the left ventricle without a significant change in stroke volume (SV). However, an excessive increase in diuresis or severe venodilation can lead to an undesirable decrease in UO and arterial hypotension (point b). Against the background of taking inotropic drugs (point c) or vasodilators that act mainly on the arteriolar bed (as well as combined vasodilators) (point d), the VR increases and the LV end-diastolic pressure decreases (due to a more complete ejection of blood during systole). Point e reflects the possible positive effect of combination therapy with inotropic and vasodilator drugs. The dotted line shows the increase in the Frank-Starling curve during therapy with inotropic and vasodilatory drugs (which, however, does not reach the level of functional activity of the normal LV)
In patients with a severe form of the disease receiving treatment in a hospital, agonists of $-adrenergic receptors (dobutamine, dopamine) are sometimes administered intravenously to temporarily maintain hemodynamic parameters. Long-term use of these drugs is limited due to the lack of oral dosage forms and rapidly developing tolerance - a progressive decrease in their therapeutic efficacy due to a decrease in the number of adrenergic receptors in the myocardium according to the feedback principle. Phosphodiesterase inhibitors are usually used in severe functional class III-IV HF requiring intravenous therapy. Despite the high efficacy 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 increase myocardial contractility, reduce LV dilatation, increase CO, and help relieve symptoms of heart failure. Against the background of taking cardiac glycosides, the sensitivity of baroreceptors increases, and, consequently, sympathetic tone decreases reflexively, which leads to a decrease in LV afterload in patients with heart failure. In addition, cardiac glycosides allow you to control the 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 inappropriate to 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. At the same time, the results of recent clinical studies indicate that therapy with β-blockers paradoxically contributes to an increase in CO and normalization of hemodynamic parameters. The mechanism of this phenomenon has not yet been studied, but it is believed that a decrease in heart rate, a weakening of sympathetic tone, and the anti-ischemic effect of β-blockers can play a positive role in these cases. Currently, the use of β-blockers in the treatment of patients with heart failure remains the subject of clinical trials.
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 with circulatory decompensation).
✧
Calcium sensitizers (levosimendan).
MECHANISM OF ACTION AND PHARMACOLOGICAL EFFECTS
Stimulantsβ
1
-adrenergic receptors
The drugs of this group, administered intravenously, affect the following receptors:
β1- adrenoceptors (positive inotropic and chronotropic action);
β2-adrenergic receptors (bronchodilation, expansion of peripheral vessels);
dopamine receptors (increased renal blood flow and filtration, dilatation of the mesenteric and coronary arteries).
A positive inotropic effect is always combined with other clinical manifestations, which can have both positive and negative effects on the clinical picture of AHF. Dobutamine - selectiveβ1- adrenomimetic, but it also has a weak effect onβ 2 - and α 1-adrenergic receptors. With the introduction of conventional doses, an inotropic effect develops, sinceβ1-stimulating effect on the myocardium prevails. A drug
does not stimulate dopamine receptors regardless of dose, therefore, renal blood flow increases only due to an increase in stroke volume.
Phosphodiesterase inhibitors.
The drugs of this subgroup, increasing myocardial contractility, also lead to a decrease in peripheral vascular resistance, which allows you to influence both preload and afterload in AHF.
calcium sensitizers.
The drug of this group (levosimendan) increases the affinity of Ca 2+
to troponin C, which increases myocardial contraction. It also has a vasodilating effect (reducing the tone of the 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 within 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 decrease in mortality, achieved in the first 2 weeks after the start of treatment, which persisted in the future (for 6 months of observation).
Levosimendan is superior to dobutamine fornii effects on blood circulation in patients with severe decompensation of CHF and low cardiac output.
INDICATIONS
Acute heart failure. Their purpose does not depend on the presence of venous congestion 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 the indicators of central hemodynamics, and also change the dose of inotropic drugs in accordance with
with the clinical picture.
Dosing
Dobutamine.
The initial infusion rate is 2–3 μg per 1 kg of body weight per minute. With the introduction of dobutamine in combination with vasodilators, control of the pulmonary artery wedge pressure is necessary. If the patient received beta-adrenergic blockers, then the action 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.
At low doses (2 μg per 1 kg of body weight per minute or less in terms of lean body weight), the drug stimulates D 1 - and D 2-receptors, which is accompanied by vasodilatation of the mesentery and kidneys and allows you to increase GFR in case of refractoriness to the action of diuretics.
In medium doses (2-5 mcg per 1 kg of body weight per minute), the drug stimulatesβ1-adrenergic receptors of the myocardium with an increase in cardiac output.
At high doses (5–10 micrograms per kg of body weight per minute), dopamine activatesα 1-adrenergic receptors, which leads to an increase in peripheral vascular resistance, LV filling pressure, tachycardia. As a rule, high doses are prescribed in emergency cases to quickly increase SBP.
Clinical features:
tachycardia is always more pronounced with dopamine compared with dobutamine;
the calculation of the dose is carried out only on lean, and not on the total body weight;
persistent tachycardia and / or arrhythmia that occurred with the introduction of a "renal dose" indicate that the rate of administration of the drug is too high.
Levosimendan.
The introduction of the drug begins with a loading dose (12–24 μg per 1 kg of body weight for 10 minutes), and then they switch to a long-term infusion (0.05–0.1 μg per 1 kg of body weight). An increase in stroke volume, a decrease in pulmonary artery wedge pressure are dose-dependent. In some cases it is possibleincreasing the dose of the drug to 0.2 μg per 1 kg of body weight. The drug is effective only in the absence of hypovolemia. Levosimendan is compatible withβ
-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 a pronounced adverse effect on the prognosis, non-glycoside inotropic drugs can only be prescribed in the form of short courses (up to 10-14 days) with a clinical picture of persistent arterial hypotension in patients with severe CHF decompensation and a reflex kidney.
SIDE EFFECTS
Tachycardia.
Supraventricular and ventricular arrhythmias.
Subsequent increase in left ventricular dysfunction (due to increased energy consumption to ensure increasing myocardial work).
Nausea and vomiting (dopamine in high doses).
Inotropic drugs are drugs that increase myocardial contractility. The most well-known inotropic drugs are 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 the blockade of the sodium-potassium "pump". As a result, the flow of sodium ions into cells increases, the exchange of sodium ions for calcium ions increases, which, in turn, causes an increase in the content of calcium ions in myocardial cells and a positive inotropic effect. In addition, glycosides slow down AV conduction and slow down heart rate (especially with atrial fibrillation) due to vagomimetic and antiadrenergic effects.
The effectiveness of glycosides in circulatory failure in patients without atrial fibrillation was not very high and was even questioned. However, specially conducted 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 III heart sound. In patients without these signs, the likelihood of an effect from the appointment of glycosides is low. Currently, digitalization is no longer applied. As it turned out, the main effect of glycosides is precisely the neurovegetative effect, which manifests itself when prescribing small doses.
In our time, indications for the appointment 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 drugs of first choice. The main cardiac glycoside is digoxin. Other cardiac glycosides are now almost never used. With tachysystolic form of atrial fibrillation, digoxin is prescribed under the control of the frequency of ventricular contractions: the goal 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 a diuretic is insufficient. In patients with sinus rhythm with heart failure, digoxin is prescribed at a dose of 1 tablet (0.25 mg) per day. At the same time, for elderly people or patients who have had a myocardial infarction, as a rule, half or even a quarter of a tablet of digoxin (0.125-0.0625 mg) per day is enough. Intravenous glycosides are prescribed extremely rarely: only in acute heart failure or decompensation of chronic heart failure in patients with 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. When taking higher doses of digoxin, an increase in mortality in patients with heart failure is observed. With 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 working capacity.
The main signs of intoxication: the occurrence of arrhythmias, loss of appetite, nausea, vomiting, weight loss. When using small doses of glycosides, intoxication develops extremely rarely, mainly when digoxin is combined with amiodarone or verapamil, which increase the concentration of digoxin in the blood. With timely detection of intoxication, temporary discontinuation of the drug with a subsequent 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 blockade), 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 severe decompensation in patients with chronic heart failure. The main non-glycoside inotropic drugs include: dopamine, dobutamine, epinephrine and norepinephrine. These drugs are administered only intravenously in order to stabilize the patient's condition, to bring him out of decompensation. After that, they switch to taking other medicines.
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, enoximone (drugs such as imobendan or vesnarinone, in addition to inhibiting phosphodiesterase, directly affect the 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 mcg/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 noted.
dopamine. The precursor of norepinephrine and promotes the release of norepinephrine from nerve endings. Dopamine receptors are located in the vessels of the kidneys, mesentery, in the coronary and cerebral arteries. Their stimulation causes vasodilation in vital organs. When infused at a rate of up to about 200 micrograms / min (up to 3 micrograms / kg / min), vasodilation is provided (“renal” dose). With an increase in the rate of dopamine infusion of more than 750 μg / min, stimulation of α-receptors and a 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 µg/min. If a higher rate of dopamine administration is needed, they try to connect dobutamine infusion or switch to norepinephrine infusion.
Dobutamine. Selective stimulator of 1-receptors (however, there is also a slight stimulation of 2- and α-receptors). With the introduction of dobutamine, a positive inotropic effect and moderate vasodilation are noted.
In refractory heart failure, dobutamine infusion is used lasting from 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 persist for 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 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.
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) with 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 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 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 solution of nitroglycerin, tachyphylaxis is possible, characterized by a decrease in the therapeutic effect in cases of repeated administration.
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). With a 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.
Table of contents for the topic "Excitability of the heart 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. Conjugation of excitation and contraction of the myocardium.
3. Cardiac cycle and its phase structure. Systole. Diastole. Asynchronous reduction phase. Isometric contraction phase.
4. Diastolic period of the ventricles of the heart. Relaxation period. Filling period. Heart preload. Frank-Starling law.
5. Activity of the heart. Cardiogram. Mechanocardiogram. Electrocardiogram (ECG). Electrodes ecg.
6. Heart sounds. First (systolic) heart sound. Second (diastolic) heart sound. Phonocardiogram.
7. Sphygmography. Phlebography. Anacrota. Catacrot. Phlebogram.
8. Cardiac output. regulation of the cardiac cycle. Myogenic mechanisms of regulation of the activity of the heart. The Frank-Starling effect.
10. Parasympathetic effects on the heart. Influence on the heart of the vagus nerve. Vagal effects on the heart.
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 the gray matter of the 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. 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 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 are located in the 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.
