1. Neural mechanism of heart’ regulation

2. Nerve and humeral regulation of heart activity. Physiology of systemic circulation regulation

3. Mechanisms of heart regulation  The aim of the circulatory regulation is to regulate the blood flow of organs to fit their metabolic requirement in different condition.  The regulation of blood flow are of three major types:  Neural  Humoral  Local

4. Cardiac innervation  Sympathetic nerve – noradrenergic fiber; Parasympathetic nerve – cholinergic fiber  Noradrenergic sympathetic nerve  to the heart increase the cardiac rate (chronotropy effect)  the force of cardiac contraction (inotropy effect).  Cholinergic vagal cardiac fibers decrease the heart rate.

5. The mechanism of catecholamines action on the heart Catecholamines, interacting with β-adrenoceptors of heart, cause activation of enzyme adenylatecyclase, which converts adenosinetryfosforic acid in cyclic adenosinemonophosphate (cAMP). Increasing of intra- cellular concentration of cAMPh causes activation of cAMPh- dependent proteinkinase, which catalyzes the phosphorylation of proteins. It leads to an increase in entrance of sodium and calcium into the cell. noradrenalin adenylate cyclase Activeted proteinkinase Not active proteinkinase Increasisng of strength of heart contractions sarcoplasmic reticulum troponin cAMPH cytoplasm adrenoreceptor ATPh

6. Catecholamines

8. The action of acetylcholine on the activity of the heart ( Effects of n. vagus on the heart) In the external membrane of cardiomyocytes muscarinic (M)-cholinergic receptors are dominated. Similarly as β-adrenoceptors, density of muscarinic receptors in the myocardium depends on the concentration of their antagonists. During interaction with muscarinic receptors Acetylcholine primarily couses inhibition of Adenylate-cyclase activity and secondary – activates Guanylate-cyclase (GC). The GC converts Huanozyn-tryfosfat into the Cyclic Guanosine-monophosphate (cGMP). Increase of intracellular concentration of cGMP causes activation of Acetylcholine dependent potassium channels. It leads to increase the of potassium ions out of the cardiomyocytes. Due to increased release of potassium occurs hyperpolarization of cell membranes. Efects: 1. negative inotropy 2. negative chronotropy 3. negative dromotropy 4. negative batmotropy acethylholine M-cholinergic receptors Hyperpolarizatin of membrane inhibition cytoplasm GC cGMP cAMP proteincinase A TP

9. Frank-Starling law Lung Scheme of heart-lung aparate by Starling Ventriculus volume Compression in aorta Venois reservoir Compresion camera Resistance regulation ce filling pressure

10. As a result the "law of the heart" (Frank- Starling law or heterometryc mechanism of regulation) was derived: the force of myocardial contraction fibers depends on their end-diastolic length. From the heart of the law implies that increased filling of the heart with blood leads to increased force of heart contractions. Reducing of the force of myocardial contraction observed when it stretched more than 25% of the initial length. Such stretching is absent in the healthy heart (only 20%). So, this act, means that the number of bridges of aktynomioze is the maximal during strain of each sarcomere to 2.2 microns. And force of cardiac contraction will depend on the number of formed bridges. The essence of the Frank-Starling law the Frank-Starling law stretching of the sarcomere FO R CE time STREINSTREIN Actine – Act Myosine – My Act My

11. Anrep's effect Increase of blood flow in aorta and so coronary arteries leads to excessive stretching surrounding myocardial cells. Increase of blood flow in aorta and so coronary arteries leads to excessive stretching surrounding myocardial cells. According to Frank Starling low cardiac contraction is directly proportional to initial length of its fibers. So increase of coronary blood flow leads to stimulation heartbeat. According to Frank Starling low cardiac contraction is directly proportional to initial length of its fibers. So increase of coronary blood flow leads to stimulation heartbeat.

12. Boudichi phenomenon In evaluation heart beat rate increase of every next heart contraction is observed. In evaluation heart beat rate increase of every next heart contraction is observed. It caused by rising of Ca2+ influx into myocardial cells without perfect outflow, because of shortening of cardio cycle duration. It caused by rising of Ca2+ influx into myocardial cells without perfect outflow, because of shortening of cardio cycle duration.

13. Bainbridge Reflex Atrial Stretch Receptors Medullary Activation (via Vagus Nerve) Increased Heart Rate Increased Sympathetic Activity to SA Node Increased Intravascular Volume Direct Stretching of SA Node

15. Effect of the cerebral cortex on heart activity Cortex is the organ of mental activity. It provides a holistic adaptive response. The work of the heart depends on the functional state of the cerebral cortex. Thus, in athletes observed pre-start condition manifesting with increasing of heart rate. Overpassing anxiety state reduction of it can be achieved. The effects of stimulation of the cerebral cortex occur during stimulation of motor and premotor zones, cingulate gyrus, orbital surface of the frontal lobe, the anterior region of the temporal lobe. Usually an increase of heart rate observed herewith. Cortex AV- node Hypothalamus Medulla Cord SA- node paravertebral symphatic ganglia Symphatic cardiac nerves

16. Effects of the hypothalamus on heart activity Cortex AV- node Hypothalamus Medulla Cord SA- node paravertebral symphatic ganglia Symphatic cardiac nerves During stimulation of different areas of the hypothalamus in anesthetized animals special points were detected. Stimulation of them accompanied by changes of the frequency and force of heart contractions. Thus, in hypothalamus are structures that regulate the activity of the heart. Often, but not always, electrical stimulation of the anterior hypothalamus leads to decreased cardiac and rear – to increase heart rate.

17. Cardiovascular centers of the brainstem Medulla oblongata is essential to Cardiovascuar centers.

18. Peculiaritiesof the vagal innervation of the heart In the medulla oblongata the nucleus of vagus nerve located. The axons of the cells of the nucleus within the right and left nerve trunks sent directed to the heart and form synapses on motor metasympatyc neurons. Right vagus nerve fibers are distributed mainly in the right atrium. The associated neurons inervate myocardium, coronary vessels and sinus-atrial node. As a result of the structural features of the right vagus nerve stimulation of it shows its influence on heart rate. Left vagus nerve fibers transmit their effects to atrioventricular node. As a result of the structural features of the left vagus nerve stimulation of it shows its influence on atrioventricular conduction and contractility of cardiomyocytes (heart rate effect). AV- node SA- node Medulla N. vagus Efects: 1. negative inotropy 2. negative chronotropy 3. negative dromotropy 4. negative batmotropy

19. Effects of n. vagus Effects of n. vagus on the heart activity. Parasympathetic stimulation causes decrease in heart rate and contractility, causing blood flow to decrease. Effects of n. vagus on the heart activity. Parasympathetic stimulation causes decrease in heart rate and contractility, causing blood flow to decrease. It is known as negative inotropic, dromotropic, bathmotropic and chronotropic effect. It is known as negative inotropic, dromotropic, bathmotropic and chronotropic effect.

20. Influence of sympathetic nervous system activity of the heart The first neurons of the sympathetic nerves that transmit impulses to the heart, located in the lateral horns of the upper four or five thoracic segments of the spinal cord (Th1-Th5). Processes of these neurons terminate in the cervical and upper thoracic sympathetic nodes, where the latter neurons, processes which go to the heart. Efects: 1. positive inotropic 2. positive chronotropic 3. positive dromotropic 4. positive batmotropnyy Cortex Hypothalamus Medulla Cord Symphatic cardiac nerves paravertebral symphatic ganglia AV- node SA- node paravertebral symphatic ganglia

21. Sympathetic effects Sympathetic nerves from Th1-5 control activity of the heart and large vessels. First neuron lays in lateral horns of spinal cord. Second neuron locates in sympathetic ganglions. Sympathetic nerve system gives to the heart vasoconstrictor and vasodilator fibers. Vasoconstrictor impulses are transmitted through alfa- adrenoreceptors, which are most spread in major coronary vessels. Transmission impulses through beta- adrenergic receptors lead to dilation of small coronary vessels. Sympathetic nerves from Th1-5 control activity of the heart and large vessels. First neuron lays in lateral horns of spinal cord. Second neuron locates in sympathetic ganglions. Sympathetic nerve system gives to the heart vasoconstrictor and vasodilator fibers. Vasoconstrictor impulses are transmitted through alfa- adrenoreceptors, which are most spread in major coronary vessels. Transmission impulses through beta- adrenergic receptors lead to dilation of small coronary vessels. Sympathetic influence produces positive inotropic, chronotropic, dromotropic, bathmotropic effects, which is increase of strength, rate of heartbeat and stimulating excitability and conductibility also. Sympathetic influence produces positive inotropic, chronotropic, dromotropic, bathmotropic effects, which is increase of strength, rate of heartbeat and stimulating excitability and conductibility also.

22. Epinephrine Norepinephrine α 1 receptor on vessels β 1 receptor on heart β 2 receptor on vessels (skeletal muscle and liver) Vasoconstriction Positive effect Vasodilation Adrenergic receptors

23. Control of heart activity by vasomotor center Lateral portion of vasomotor center transmit excitatory signals through sympathetic fibers to heart to increase its rate and contractility. Lateral portion of vasomotor center transmit excitatory signals through sympathetic fibers to heart to increase its rate and contractility. Medial portion of vasomotor center transmit inhibitory signals through parasympathetic vagal fibers to heart to decrease its rate and contractility. Neurons, which give impulses to the heart, have constant level of activity even at rest, which is characterized as nervous tone. Medial portion of vasomotor center transmit inhibitory signals through parasympathetic vagal fibers to heart to decrease its rate and contractility. Neurons, which give impulses to the heart, have constant level of activity even at rest, which is characterized as nervous tone.

25. Location and innervation of arterial baroreceptors

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