Mechanical Heart Functioning

MECHANICAL HEART FUNCTIONING

Heart Sounds - Auscultation is performed through the Stethoscope. This technique listens for sounds of the heartbeat coming from turbulence in blood flow caused by valve closure. The first heart sound (LUB) is created with the closing of the atrioventricular valves. We hear the tricuspid valve and the ventricle start to contract. The second heart sound (DUB) is created with the closing of semilunar valves. When the contraction is over, the pulmonary and aortic valves are closed in order to prevent the backflow from the aorta and from the pulmonary artery.

Heart sound in a normal subject: LUB-DUB

At the end of the ejection phase, the semilunar valves (the aortic valve – here not visible – and the pulmonary valve) close. Heart sound DUB. AV valves (mitral and tricuspid valves) close. Heart sound LUB.

Coronary Arteries and Veins

Coronary Arteries - Branches of the aorta above the aortic semilunar valve. The left coronary artery is split into:

circumflex branch (LCx): in coronary sulcus, supplies left- atrium and left ventricle; anterior interventricular artery (LAD): supplies both ventricles

Right coronary artery (RCA) is splitted into: marginal branch: in coronary sulcus, supplies- right ventricle and posterior interventricular artery: supplies both ventricles.

If there are some problems connected to the coronary artery, part of the heart has a lack of blood and this phenomena Is called ISCHEMIA.

Coronary Veins - Collects wastes from cardiac muscle. Drains into a large sinus on posterior surface of heart called the coronary sinus. Coronary sinus is important for the introduction of electrodes during electrophysiological studies. Coronary sinus empties into right atrium.

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Coronary arteries and veins – learn to recognise following patterns

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Innervation of the HeartInformation about blood pressure, generated by baroreceptors in the carotid sinuses and in the aortic arch,

Travels via afferent fibers in cranial nerves IX and X to the cardiovascular centre of the autonomic nervous system in the brain stem. This centre responds dynamically by adjusting efferent sympathetic outflow (travelling to the heart via the spinal cord), and adjusting efferent parasympathetic outflow (travelling to the heart via cranial nerve X). Thus, heart rate and cardiac contractility are adjusted to counteract blood pressure changes.

From the book: Autonomic innervation of the heart plays an important role in regulating cardiac function. The heart is innervated by parasympathetics (vagal) and sympathetic efferent fibers. The right vagus nerve preferentially innervates the sinoatrial (SA) node, whereas the left vagus nerve innervates the AV node; however, significant overlap can occur in the anatomical distribution. Atrial muscle is also innervated by vagal efferent; the ventricular myocardium is only sparsely innervated by vagal efferent. Sympathetic efferent nerves are present.

throughout the atria (especially in the SA node) and ventricles, and in the conduction system of the heart. Vagal activation of the heart decreases heart rate (negative chronotropy), decreases conduction velocity (negative dromotropy), and decreases contractility (negative inotropy) of the heart. Vagal-mediated inotropic influences are moderate in the atria and relatively weak in the ventricles. Activation of the sympathetic nerves to the heart increases heart rate, conduction velocity, and inotropy. Sympathetic influences are pronounced in both the atria and ventricles. 7 MECHANICAL HEART FUNCTIONING 10 - Mechanical Heart Function: Contraction Mechanism The contraction mechanism is one of the determinants of the mechanical heart functions. Cardiac functions are determined by different factors: 1. Contraction mechanism 2. Excitation-Contraction: calcium influences on the contraction. 3. Electrical activity 4. Neurohormonal systems: they exert their influence on contractility. 5. Cardiovascular

Interactions & Loading conditions: are pre-load after-load sohow will the heart fill, which pressure will the heart see when it pumps the blood in the aorta and pulmonary arteries. These are all together called the loading conditions and they have an important impact in cardiac function.

Geometry and anatomy are relevant. All these factors come together all these determinants resulting in a specific pump function for a specific person in specific conditions.

From the sarcomere to the heart, from shortening to ejection – if we want to understand contraction of the heart we have to discuss mechanisms and anatomy from the microscopic to macroscopic. Starting with myofilaments (contractile proteins) that are in the sarcomeres (contractile unite). Many sarcomeres form together myofibrils that are in myocytes. Myocytes all together joined by intercalated discs form myofibers and finally these form the myocardium and the beating heart.

With this technique we can clearly see several important parts of the cell. First we have here the connection between cells to desmosomes, then most of the time about here are the gap junction is located but you cannot see them. The mitochondria in the cell is an important structure also called the powerhouse of the cell where ATP production (fuel of the cell) occurs. Sarcomeres are contractile elements (proteins). Sarcomeres are located between to Z lines (you don't have to know all the names of all these lines of bands). Thin filament is called Actin, thick filaments are myosin. Contraction and relaxation happens by sliding of these two filaments, the contraction is an active process while relaxation is a passive one.

Thin filament - Zooming in a bit more, actin is a spherical protein of tropomyosin, string like structure and of the regulatory troponin complex. This regulatory troponin complex is called regulatory because it controls the movement of the tropomyosin between two states.

It deletes covers binding sites or it freezes the myosinbinding sites. The regulatory troponin complex is freeing these binding-sites when calcium is bound to thetroponin complex. That's the condition for the formation of cross branches with myosin heads that attachedto the myosin binding sites.

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Thick and thin filament, Crossbridge - The myosin filament (thick filament) consists of about 300 to 400myosin molecules, with myosin heads that combined to the myosin binding sites on the thin filament on theactin. Myosin state where there is a binding between the myosin head and the thin filament this binding iscalled crossbridge. Along this thick filament, every 14.3 nanometres, there are myosin binding sites; somultiple cross bridges are possible.

Calcium initiates cross-bridge formation – When calcium binds to troponin complex, the latter changesshape and takes the tropomyosin away from the binding sites. The figure up is the situation before

Binding: where the troponin complex has its original shape. Down, the calcium binds to the troponin complex, that complex changes its shape and takes the tropomyosin away from the binding sites, making it possible for the myosin head to bind the actin.

Cross-Bridge Cycle: 9 MECHANICAL HEART FUNCTIONING

Cross bridge cycle: it describes the condition in which the sarcomeres make the contraction and relaxation. ATP is the fuel and needed for contraction. However, ATP is also needed for relaxation (it causes actin-myosin dissociation). Hence, lack of ATP during ischemia contributes to a decrease in systolic and in diastolic functioning of the heart. Without ATP myosin cannot detach and the muscles cannot relax. After hydrolyzation of ATP in ADP, there is a cocked state (state of activation) where the myosin can do its work. Thanks to calcium (on the regulating troponin complex) the binding between actin and myosin is possible at the binding site and a crossbridge is formed (3). Power stroke is

Possible when the inorganic phosphate is released. The Power stroke causes sliding of the filaments and when the PS is over the ADP is released too and the filaments will return to the start position.

Remember: ATP is needed for contraction and for relaxation, and Calcium is needed to start crossbridge formation, power stroke and contraction.

Titin

Titin is a giant protein that connects the Z line to the M line in the sarcomere. It acts as a molecular spring in the I-band and is responsible for the passive elasticity of muscle. Initial stretching of the sarcomere first aligns the structures in the I band, except for the PEVK region, higher stretching forces also stretch the PEVK region.

Isomeric Force-Length Relationship

An essential property of the heart is isomeric Force-Length Relationship (that is in common with all the other kind of muscles). Imagine the heart is filling passively (condition after contraction) because of the difference of pressures btw atria and the ventricles, so the

ventricle (curva inferiore A) aumenta di dimensioni all'interno della lunghezza del sarcomero. Quindi, la pressione (la forza) che il muscolo sviluppa qui è passiva ed è determinata, tra le altre cose, dalle proprietà della titina. Dato un certo grado di pre-stiramento (ad esempio, la situazione L2) quando attiviamo il cuore ma non permettiamo che espella alcun tipo di sangue (bloccando l'aorta e l'arteria polmonare), nel grafico a destra vediamo la curva normalizzata della forza nel tempo, dove è presente la massima forza sviluppata dal cuore. Questa massima forza è riportata nel grafico a sinistra e ciò che vediamo è che con diversi valori di pre-stiramento (diverse lunghezze del sarcomero) la massima forza sviluppata aumenta, e questo viene chiamato Relazione Forza-Lunghezza Isometrica di Picco. È una proprietà importante per il cuore perché significa che un cuore riempito con una maggiore quantità di sangue è più forte e quindi in grado di pompare di più. 10 FUNZIONAMENTO MECCANICO DEL CUORE Sovrapposizione actina-miosina dipendente dallo stiramento - Lo stiramento del

sarcomere influences the actin that is‘useful’.

Situation 1: actin and myosin are non-overlapping: the crossbridge is impossible.

Situation 6: complete overlapping, the muscle cannot contract so also here the situation is bad.

(a sx) the optimum value is the maximum of the curve.

Frank-Starling’s “Law of the heart” - Cardiac stroke volume increases with increased filling before contraction starts. This is fundamental to understand the function of the heart in the circulation.

It is also called “Starling’s law” (Linacre Lecture, 1915), “Frank-Starling mechanism”, “Legge del cuore” or “Legge di Maestrini” (Dario Maestrini, 1886-1975)

I is interested in sarcomere force-length relationship, possible mechanisms:

• Optimal actin-myosin overlap (left part of the curva mostrata sopra)
• Reduced lattice spacing
• Altered myosin head orientation
• Increased Ca sensitivity

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11 – Medical

Heart Function: Excitation-Contraction Coupling

Excitation-contraction coupling -