Developing small syndrome cardiac output . This is expressed in a decrease in blood pressure, a drop in pulse, tachycardia, and pale skin.

Systolic volume is the amount of blood that enters the circulation during one ventricular contraction. Minute volume is the amount of blood that flows through the aorta in one minute. Systolic volume is determined in the clinic in such a way that minute volume is measured and divided by the number of heart contractions per minute. Under physiological conditions, the systolic and minute volumes of the right and left ventricles are almost the same. The value of minute volume in healthy individuals is primarily determined by the body's need for oxygen. Under pathological conditions, the body's need for oxygen should also be satisfied, but it often cannot be satisfied even with a significant increase in cardiac output.

In healthy individuals, minute volume at rest is almost constant over a long period of time and is proportional to the surface of the body, expressed in square meters. The number indicating the minute volume per m2 of body surface is called the “cardiac indicator”. The value established by Grollmann of 2.2 liters was used for a long time as a cardiac indicator. The figure calculated by Cournand based on data obtained by cardiac catheterization is higher: 3.12 liters per minute per 1 m2 of body surface. In the future we will use cardiac indicator Kournana. If we want to determine the ideal minute volume of a child, then we determine the body surface from the Dubois table and multiply the resulting value by 3.12 and thus obtain the minute volume in liters.

Previously, minute volume was compared with body weight. The incorrectness of this approach, especially in pediatrics, is clear, because the body surface of infants and small children is large compared to their weight, and accordingly their minute volume is relatively larger.
Body surface (in m2) of healthy children of various ages, number pulse beats per minute, minute volume, systolic volume and average blood pressure, corresponding to age, are given in table 2. These tables are averages, and in life there are many individual deviations. It turns out that the minute volume of an average-weight newborn, which is 560 ml, increases almost tenfold in an adult. In the case of average development, during the same time the surface of the body also increases tenfold, and the two values ​​are thus parallel. During this time, a person’s body weight increases 23 times. The table shows that in parallel with the increase in cardiac output, the number of heartbeats per minute decreases. Thus, during growth, systolic volume necessarily increases to a greater extent than cardiac output, which increases in proportion to the increase in body surface. The body surface area and minute volume of the average newborn increase 10-fold in an adult, while systolic volume increases 17-fold.

During individual contractions of the heart, the blood in the ventricles is not completely expelled, and the amount of blood remaining there can, under normal circumstances, reach the amount of systolic volume. Under pathological conditions, significant amounts may remain in the ventricles large quantity blood than which is expelled during systole. A number of attempts have been made to determine the amount of residual blood, partly using x-ray examination, partly by the use of paints. According to research by Harmon and Nyulin, there is a close relationship between blood circulation time and the amount of blood remaining in the ventricles during systole.

The minute volume of a healthy person and under physiological conditions depends on a number of factors. Muscular work increases it 4-5 times, in extreme cases on a short time 10 times. Approximately 1 hour after eating, the minute volume becomes 30-40% greater than it was before, and only after about 3 hours does it reach its original value. Fear, fright, excitement - probably due to the development large quantities adrenaline - increase minute volume. At low temperatures, cardiac activity is more economical than at higher temperatures. high temperature. Temperature fluctuations of 26°C do not have a significant effect on minute volume. At temperatures up to 40° C it increases slowly, and above 40° C it increases very quickly. The minute volume is also affected by the position of the body. When lying down it decreases, and when standing it increases. Other data on the increase and decrease in cardiac output are given partly in the chapter on decompensation, and partly in the chapters examining individual pathological conditions.

The heart is able to increase its minute volume in three ways: 1. by increasing the number of pulse beats with the same systolic volume, 2. by increasing the systolic volume with the same number of pulse beats, 3. simultaneous increase systolic volume and pulse rate.

As the pulse rate increases, the minute volume increases only if the venous blood flow also increases accordingly, otherwise the ventricle contracts after insufficient filling, and thus, due to the decrease in systolic volume, the minute volume does not increase. At very severe tachycardia the filling may be so imperfect (for example, when acute failure coronary circulation, with paroxysmal tachycardia), that, despite the high heart rate, minute volume decreases.

The child’s heart is able to increase the number of contractions per minute without harm from 100 to a maximum of 150-200. With an unchanged systolic volume, the minute volume can thus increase only 1.5-2 times. If a greater increase is required, cardiac output is increased by simultaneous dilatation of the heart.

If, as a result of an abundant flow of venous blood in the large veins and atria, there is sufficient quantity blood to fill the ventricles, then during diastole more blood enters the ventricles, and more high pressure in the ventricles increases systolic volume according to Starling's law. Thus, minute volume increases without increasing heart rate. In humans, this phenomenon is observed mainly during hypertrophy of the heart muscle; in childhood it is rare. A small heart is not able to accommodate more than a certain amount of blood, especially since an increase in atrial pressure very soon causes an increase in the pulse rate through the Bainbridge reflex. In infancy and childhood There is already a greater tendency to tachycardia, and thus tachycardia plays a greater role in increasing cardiac output than increasing dilatation. The ratio of these two factors is determined individual characteristics, where the greatest role, of course, belongs to influences from the nervous and hormonal systems. Hamilton's work and West and Taylor's review abstract lay out it very well physiological changes minute volume and external and internal factors influencing it.

If the body's need for oxygen cannot be satisfied by increasing cardiac output, tissues take up more oxygen from the blood than usual.

Systolic (stroke) blood volume is the amount of blood that the heart pumps into the corresponding vessels with each ventricular contraction.

The greatest systolic volume is observed at a heart rate from 130 to 180 beats/min. At heart rates above 180 beats/min, systolic volume begins to decrease significantly.

With a heart rate of 70 - 75 per minute, the systolic volume is 65 - 70 ml of blood. In a person with a horizontal body position under resting conditions, the systolic volume ranges from 70 to 100 ml.

At rest, the volume of blood ejected from the ventricle is normally between one-third and one-half of the total amount of blood contained in this chamber of the heart at the end of diastole. The reserve blood volume remaining in the heart after systole is a kind of depot, providing an increase in cardiac output in situations in which rapid intensification of hemodynamics is required (for example, during physical activity, emotional stress and etc.).

Minute blood volume (MBV) - the amount of blood pumped by the heart into the aorta and pulmonary trunk in 1 min.

For conditions of physical rest and horizontal position body of the test subject, normal IOC values ​​correspond to the range of 4-6 l/min (values ​​of 5-5.5 l/min are more often given). The average values ​​of the cardiac index range from 2 to 4 l/(min. m2) - values ​​of the order of 3-3.5 l/(min. m2) are more often given.

Since the human blood volume is only 5-6 liters, the complete circulation of the entire blood volume occurs in approximately 1 minute. During periods of heavy work, the IOC in a healthy person can increase to 25-30 l/min, and in athletes - up to 35-40 l/min.

In the oxygen transport system, the circulatory apparatus is the limiting link, therefore the ratio of the maximum value of IOC, manifested during maximally intense muscular work, with its value under basal metabolic conditions gives an idea of ​​the functional reserve of the entire cardiovascular system. vascular system. The same ratio also reflects the functional reserve of the heart itself in terms of its hemodynamic function. Hemodynamic functional reserve of the heart in healthy people is 300-400%. This means that resting IOC can be increased by 3-4 times. In physically trained individuals, the functional reserve is higher - it reaches 500-700%.

Factors influencing systolic volume and cardiac output:

• 1. body weight, which is proportional to the weight of the heart. With a body weight of 50 - 70 kg - heart volume is 70 - 120 ml;
• 2. the amount of blood flowing to the heart (venous return of blood) - the greater the venous return, the greater the systolic volume and minute volume;
• 3. The strength of heart contraction affects systolic volume, and frequency affects minute volume.

Basic physiological function The heart is pumping blood into the vascular system.

The amount of blood ejected by a ventricle of the heart per minute is one of the most important indicators functional state hearts and is called minute volume of blood flow, or minute volume of the heart. It is the same for the right and left ventricles. When a person is at rest, the minute volume averages 4.5-5.0 liters. By dividing the minute volume by the number of heartbeats per minute, you can calculate systolic volume blood flow With a heart rate of 70-75 per minute, the systolic volume is 65-70 ml of blood. Determination of the minute volume of blood flow in humans is used in clinical practice.

Most exact way determination of the minute volume of blood flow in humans was proposed by Fick (1870). It consists of indirectly calculating the cardiac output, which is done by knowing: 1) the difference between the oxygen content in arterial and venous blood; 2) the volume of oxygen consumed by a person per minute. Let's say
that in 1 minute 400 ml of oxygen entered the blood through the lungs, every
100 ml of blood absorbs 8 ml of oxygen in the lungs; therefore, in order to assimilate everything
the amount of oxygen that entered the blood through the lungs per minute (in our case
at least 400 ml), it is necessary that 100 * 400/8 = 5000 ml of blood pass through the lungs. This

the amount of blood is the minute volume of blood flow, which in this case is 5000 ml.

When using the Fick method, you must take venous blood from the right side of the heart. IN last years venous blood from a person is taken from the right half of the heart using a probe inserted into right atrium through the brachial vein. This method of drawing blood is not widely used.

A number of other methods have been developed to determine minute, and therefore systolic, volume. Currently, some paints and radioactive substances are widely used. A substance injected into a vein passes through right heart, pulmonary circulation, left heart and enters the arteries great circle, where its concentration is determined. At first it increases in waves and then falls. After some time, when a portion of blood containing its maximum amount passes through the left heart a second time, its concentration is arterial blood again increases slightly (the so-called recirculation wave). The time from the moment of administration of the substance to the beginning of recirculation is noted and a dilution curve is drawn, i.e., changes in the concentration (increase and decrease) of the test substance in the blood. Knowing the amount of a substance introduced into the blood and contained in the arterial blood, as well as the time required for the passage of the entire amount of the injected substance through the circulatory system, we can calculate the minute volume (MV) of blood flow in l/min using the formula:

where I is the amount of administered substance in milligrams; C is its average concentration in milligrams per 1 liter, calculated from the dilution curve; T- duration of the first circulation wave in seconds.

Currently, a method has been proposed integral rheography. Rheography (impendanceography) is a method of recording the electrical resistance of tissues of the human body electric current passed through the body. To avoid causing tissue damage, currents of ultra-high frequency and very low strength are used. Blood resistance is much less than tissue resistance, so increasing the blood supply to tissues significantly reduces their electrical resistance. If we record the total electrical resistance chest in several directions, then periodic sharp decreases in it occur at the moment the heart ejects systolic blood volume into the aorta and pulmonary artery. In this case, the magnitude of the decrease in resistance is proportional to the magnitude of the systolic ejection.

Keeping this in mind and using formulas that take into account body size, constitutional features, etc., it is possible to determine the value of systolic blood volume using rheographic curves, and multiplying it by the number of heartbeats to obtain the value of cardiac output.

Systolic and minute blood volumes

The amount of blood ejected by a ventricle of the heart into an artery per minute is important indicator functional state of the cardiovascular system (CVS) and is called minute volume blood (IOC). It is the same for both ventricles and at rest is 4.5-5 liters. If we divide the IOC by heart rate per minute we get systolic volume (CO) of blood flow. With a heart contraction of 75 beats per minute, it is 65-70 ml; during work it increases to 125 ml. In athletes at rest it is 100 ml, during work it increases to 180 ml. The determination of IOC and CO is widely used in the clinic, which can be done by calculation using indirect indicators (using the Starr formula, see Workshop on Normal Physiology).

The volume of blood in the ventricular cavity that it occupies before its systole is end-diastolic volume (120-130 ml).

The volume of blood remaining in the chambers after systole at rest is reserve and residual volumes. The reserve volume is realized when CO increases under load. Normally, it is 15-20% of end-diastolic.

The volume of blood in the cavities of the heart remaining when the reserve volume is fully realized at maximum systole is residual volume. Normally, it is 40-50% of end-diastolic. CO and IOC values ​​are not constant. During muscular activity, IOC increases to 30-38 l due to increased heart rate and increased CO2.

The IOC value divided by the body surface area in m2 is determined as cardiac index(l/min/m2). It is an indicator of the pumping function of the heart. Normally, the cardiac index is 3-4 l/min/m2. If the IOC and blood pressure in the aorta are known (or pulmonary artery) it is possible to determine the external work of the heart

P = MO x BP

P - heart work per minute in kilograms (kg/m).

MO - minute volume (l).

Blood pressure is pressure in meters of water column.

At physical rest, the external work of the heart is 70-110 J, during work it increases to 800 J, for each ventricle separately. The entire complex of manifestations of cardiac activity is recorded using various physiological techniques - cardiographs: ECG, electrokymography, ballistocardiography, dynamocardiography, apical cardiography, ultrasound cardiography, etc.

Diagnostic method for the clinic is the electrical registration of the movement of the contour of the heart shadow on the screen of the X-ray machine. A photocell connected to an oscilloscope is applied to the screen at the edges of the heart contour. As the heart moves, the illumination of the photocell changes. This is recorded by an oscilloscope in the form of a curve of contraction and relaxation of the heart. This technique is called electrokymography.

Apical cardiogram recorded by any system that detects small local movements. The sensor is fixed in the 5th intercostal space above the site of the cardiac impulse. Characterizes all phases cardiac cycle. But it is not always possible to register all phases: the cardiac impulse is projected differently, and part of the force is applied to the ribs. Sign up with different persons and it may differ from one person to another, depending on the degree of development of the fat layer, etc.

The clinic also uses research methods based on the use of ultrasound - ultrasound cardiography.

Ultrasonic vibrations at a frequency of 500 kHz and higher penetrate deeply through tissues being generated by ultrasound emitters applied to the surface of the chest. Ultrasound is reflected from tissues of various densities - from the outer and inner surface heart, from blood vessels, from valves. The time it takes for the reflected ultrasound to reach the capturing device is determined.

If the reflective surface moves, the return time of the ultrasonic vibrations changes. This method can be used to record changes in the configuration of heart structures during its activity in the form of curves recorded from the screen of a cathode ray tube. These techniques are called non-invasive.

TO invasive techniques relate:

Catheterization of the heart cavities. An elastic catheter probe is inserted into the central end of the opened brachial vein and pushed towards the heart (into its right half). A probe is inserted into the aorta or left ventricle through the brachial artery.

Ultrasound scanning - the ultrasound source is inserted into the heart using a catheter.

Angiography is a study of heart movements in the field x-rays and etc.

Thus, the work of the heart is determined by 2 factors:

1. The amount of blood flowing to it.

2. Vascular resistance during the expulsion of blood into the arteries (aorta and pulmonary artery). When the heart cannot pump all the blood into the arteries at a given vascular resistance, heart failure occurs.

There are 3 types of heart failure:

Failure from overload when the heart is normal contractility Excessive demands are made for defects and hypertension.

Heart failure due to myocardial damage: infections, intoxications, vitamin deficiencies, violation coronary circulation. At the same time, it decreases contractile function hearts.

Mixed form insufficiency - with rheumatism, dystrophic changes in the myocardium, etc.

5. Regulation of cardiac activity

Adaptation of heart activity to the changing needs of the body is carried out using regulatory mechanisms:

Myogenic autoregulation.

Nervous mechanism regulation.

Humoral mechanism regulation.

Myogenic autoregulation. The mechanisms of myogenic autoregulation are determined by the properties of cardiac muscle fibers. Distinguish intracellular regulation. Mechanisms for regulating protein synthesis operate in each cardiomyocyte. With increasing load on the heart, there is an increase in the synthesis of contractile proteins of the myocardium and the structures that ensure their activity. In this case, physiological hypertrophy of the myocardium occurs (for example, in athletes).

Intercellular regulation. Associated with the function of nexuses. Here, impulses are transmitted from one cardiomyocyte to another, substances are transported, and myofibrils interact. Some of the mechanisms of self-regulation are associated with reactions that occur when the initial length of myocardial fibers changes - heterometric regulation and reactions not related to changes in the initial length of myocardial fibers - homeometric regulation.

The concept of heterometric regulation was formulated by Frank and Starling. It was found that the more the ventricles stretch during diastole (up to a certain limit), the stronger their contraction in the next systole. Increased filling of the heart with blood, caused by an increase in its inflow or a decrease in the release of blood into the vessels, leads to stretching of the myocardial fibers and an increase in the force of contractions.

Homeometric regulation includes effects associated with changes in pressure in the aorta (Anrep effect) and changes in heart rate (effect or Bowditch ladder). Anrep effect is that an increase in pressure in the aorta leads to a decrease in systolic ejection and an increase in the residual blood volume in the ventricle. The incoming new volume of blood leads to stretching of the fibers, heterometric regulation is activated, which leads to increased contraction of the left ventricle. The heart is freed from excess residual blood. The equality of venous inflow and cardiac output is established. In this case, the heart, ejecting against the increased resistance in the aorta the same volume of blood as at lower pressure in the aorta, performs increased work. With a constant contraction frequency, the power of each systole increases. Thus, the force of contraction of the ventricular myocardium increases in proportion to the increase in resistance in the aorta - the Anrep effect. Hetero- and homeometric regulation (both mechanisms) are interconnected. Bowditch effect is that the strength of myocardial contractions depends on the rhythm of contractions. If an isolated, stopped frog heart is subjected to rhythmic stimulation with an ever-increasing frequency, then the amplitude of contractions for each subsequent stimulus gradually increases. The increase in the strength of contractions for each subsequent stimulus (up to a certain value) is called the Bowditch “phenomenon” (ladder).

Intracardiac peripheral reflexes are closed in the intramural (intraorgan) ganglia of the myocardium. This system includes:

1. Afferent neurons form mechanoreceptors on myocytes and caronary vessels.

2. Interneurons.

3. Efferent neurons. Innervates the myocardium and coronary vessels. These links form intracardiac reflex arcs. So, with increasing stretching of the right atrium (if the blood flow to the heart increases), the left ventricle contracts intensely. The release of blood accelerates, freeing up space for newly flowing blood. These reflexes are formed in ontogenesis early before the appearance of central reflex regulation.

Extracardiac nervous regulation. Most high level adaptation of the cardiovascular system is achieved neurohumoral regulation. Nervous regulation carried out by the central nervous system through the sympathetic and vagus nerves.

Influence vagus nerve . From the nucleus of the vagus nerve, located in the medulla oblongata, axons depart as part of the right and left nerve trunks, approach the heart and form synapses on motor neurons intramural ganglia. The fibers of the right vagus nerve are distributed mainly in the right atrium: they innervate the myocardium, coronary vessels, and SA node. The fibers of the left innervate mainly the AV node and influence the conduction of excitation. Research by the Weber brothers (1845) established the inhibitory effect of these nerves on the activity of the heart.

When irritating the peripheral end of the cut vagus nerve, the following changes were revealed:

1. Negative chronotropic effect (slowing down the rhythm of contractions).

2. Negative inotropic the effect is a decrease in the amplitude of contractions.

3. Negative bathmotropic the effect is a decrease in myocardial excitability.

4. Negative dromotropic the effect is a decrease in the speed of excitation in cardiomyocytes.

Irritation of the vagus nerve can cause a complete stop of cardiac activity, which occurs complete blockade conducting excitation in the AV node. However, as stimulation continues, the heart resumes contractions, and slipping away heart from the influence of the vagus nerve.

Effects of the sympathetic nerve. The first neurons of the sympathetic nerves are located in the lateral horns of the 5 upper segments thoracic spinal cord. Second neurons from the cervical and upper thoracic sympathetic nodes go mainly to the ventricular myocardium and conduction system. Their effect on the heart was studied by I.F. Zion. (1867), I.P. Pavlov, W. Gaskell. Their opposite effect on the activity of the heart was established:

1. Positive chronotropic effect (increased heart rate).

2. Positive inotropic effect (increased contraction amplitude).

3. Positive bathmotropic effect (increased myocardial excitability).

4. Positive dromotropic effect (increasing the speed of excitation). Pavlov identified sympathetic branches that selectively increase the force of heart contraction. By stimulating them, it is possible to remove the blockade of excitation in the AV node. Improvement in the conduction of excitation under the influence of the sympathetic nerve concerns only the AV node. The interval between contraction of the atria and ventricles is shortened. An increase in myocardial excitability is observed only if it was previously reduced. When the sympathetic and vagus nerves are simultaneously stimulated, the action of the vagus predominates. Despite the opposing influences of the sympathetic and vagus nerves, they are functional synergists. Depending on the degree of filling of the heart and coronary vessels blood, the vagus nerve can also have the opposite effect, i.e. not only slow down, but also enhance the activity of the heart.

The transfer of excitation from the endings of the sympathetic nerve to the heart is carried out using a mediator norepinephrine. It breaks down more slowly and lasts longer. At the endings of the vagus nerve it is formed acetylcholine. It is quickly destroyed by ACh esterase, so it only has local action. When both nerves (sympathetic and vagus) are transected, a higher rhythm of the AV node is observed. Consequently, his own rhythm is much higher than under the influence nervous system.

Nerve centers medulla oblongata, from which the vagus nerves extend to the heart, are in a state of constant central tone. From them constant inhibitory influences come to the heart. When both vagus nerves are cut, heart contractions increase. The following factors influence the tone of the vagus nerve nuclei: increased levels of adrenaline, Ca 2+ ions, and CO 2 in the blood. Breathing influences: when inhaling, the tone of the vagus nerve nucleus decreases, when exhaling, the tone increases and heart activity slows down (respiratory arrhythmia).

Regulation of cardiac activity is carried out by the hypothalamus, limbic system, cortex cerebral hemispheres brain.

Important role receptors of the vascular system play in the regulation of the heart, forming vascular reflexogenic zones.

The most significant: aortic, sinocarotid zone, pulmonary artery zone, the heart itself. The mechano- and chemoreceptors included in these zones are involved in stimulating or slowing down the activity of the heart, which leads to an increase or decrease in blood pressure.

Excitation from the receptors of the mouths of the vena cava leads to increased frequency and intensification of heart contractions, which is associated with a decrease in the tone of the vagus nerve, an increase in the tone of the sympathetic - Bainbridge reflex. The classic vagal reflex includes the reflex Goltz. At mechanical impact cardiac arrest is observed in the stomach or intestines of the frog (the influence of the vagus nerve). In humans, this is observed when there is a blow to the anterior abdominal wall.

Oculocardiac reflex Danini-Aschner. When pressing on eyeballs there is a decrease in heart contractions by 10–20 per minute (the influence of the vagus nerve).

An increase in heart rate and contractions is observed during pain, muscle work, and emotions. The participation of the cortex in the regulation of the heart is proven by the method conditioned reflexes. If you combine it many times conditioned stimulus(sound) with pressure on the eyeballs, which leads to a slowdown in heart contractions, then after a while only the conditioned stimulus (sound) will cause the same reaction - conditioned ocular-heart reflex Danini-Aschner.

With neuroses, disturbances may also appear in the cardiovascular system, which are established as pathological conditioned reflexes. Signals from the muscle proprioceptors. At muscle loads impulses from them have an inhibitory effect on the vagal centers, which leads to increased heart contractions. The rhythm of heart contractions can change under the influence of excitement from thermoreceptors. Increased body temperature or environment causes increased contractions. Cooling of the body upon entering cold water, when bathing, leads to a decrease in contractions.

Humoral regulation. It is carried out by hormones and ions of intercellular fluid. Stimulate: catecholamines (adrenaline and norepinephrine), increase the strength and rhythm of contractions. Adrenaline interacts with beta receptors, adrenylate cyclase is activated, cyclic AMP is formed, inactive phosphorylase turns into active, glycogen is broken down, glucose is formed, and as a result of these processes energy is released. Adrenaline increases the permeability of membranes to Ca 2+, which is involved in the processes of contraction of cardiomyocytes. Glucagon, corticosteroids (aldosterone), angiotensin, serotonin, thyroxine also affect the force of contraction. Ca 2+ increases the excitability and conductivity of the myocardium.

Acetylcholine, hypoxemia, hypercapnia, acidosis, K + ions, HCO -, H + ions inhibit cardiac activity.

For normal heart activity great importance have electrolytes. The concentration of K + and Ca 2+ ions affects the automaticity and contractile properties of the heart. Excess K + causes a decrease in rhythm, contraction force, and a decrease in excitability and conductivity. Washing the isolated heart of animals with a concentrated solution of K + leads to relaxation of the myocardium and cardiac arrest in diastole.

Ca 2+ ions speed up the rhythm, increase the strength of heart contractions, excitability, and conductivity. Excess Ca 2+ leads to cardiac arrest in systole. Disadvantage - weakens heart contractions.

The role of the higher parts of the central nervous system in the regulation of cardiac activity

The cardiovascular system through the suprasegmental sections of the autonomic nervous system - the thalamus, hypothalamus, and cerebral cortex, it is integrated into the behavioral, somatic, and autonomic reactions of the body. The influence of the cerebral cortex (motor and premotor zones) on the circulatory center of the medulla oblongata underlies conditioned reflex cardiovascular reactions. Irritation of the central nervous system structures is usually accompanied by an increase in heart rate and an increase in blood pressure.