1. CARDIAC MUSCLE Three types of cardiac muscle exist: -Atrial muscle (contractile); - ventricular muscle (contractile); -specialized muscle fibers (excitatory and conductive). CIRCULATION The HEART

2. SPECIAL PROPERTIES OF CARDIAC MUSCLE Syncytium: There are intercalated discs between muscle fibers (unlike skeletal muscle). Electrical resistance through them is very low (only 1/400 the resistance of the cell membrane) because they have permeable gap junctions (free diffusion of ions). So action potential (AP) travels from one cardiac muscle cell to another (unlike skeletal muscle). There are atrial syncytium and ventricular syncytium in the heart.

3. NOTE: the atria are separated from the ventricles by fibrous tissue (atrioventricular septum). This allows the atria to contract ahead of ventricles. AP can be conducted from the atrial syncytium into the ventricular syncytium only by way of a specialized conductive system (the atrioventricular bungle). NOTE: the atria are separated from the ventricles by fibrous tissue (atrioventricular septum). This allows the atria to contract ahead of ventricles. AP can be conducted from the atrial syncytium into the ventricular syncytium only by way of a specialized conductive system (the atrioventricular bungle). Owing to the syncytial structure all cells of syncytium are excited and participate in contractile response (to each threshold and super-threshold stimulus). So strength of cardiac contraction does not depend on strength of stimulus (principle “all or none”)- unlike skeletal muscle. Owing to the syncytial structure all cells of syncytium are excited and participate in contractile response (to each threshold and super-threshold stimulus). So strength of cardiac contraction does not depend on strength of stimulus (principle “all or none”)- unlike skeletal muscle.

5. Recording the depolarization wave (A and B) and the repolarization wave (C and D) from a cardiacmuscle fiber.

6. Above, Monophasic action potential from a ventricular muscle fibboer during normal cardiac function, showing rapid depolarization and then repolarization occurring slowly during the plateau stage but rapidly toward the end. Below, Electrocardiogram recorded simultaneously.

7. Membrane potential The resting MP of normal cardiac muscle is about –90 mv (because of high K- permeability and low Na-permeability of the cell membrane). The resting MP of normal cardiac muscle is about –90 mv (because of high K- permeability and low Na-permeability of the cell membrane). Action potential is spike from –90 mv to +20 mv (positive portion of AP is called “overshoot potential”). Action potential is spike from –90 mv to +20 mv (positive portion of AP is called “overshoot potential”).

8. NOTE: membrane of ventricular cell remains depolarized about 300 msec (unlike skeletal muscle). This prolonged phase of depolarization is called “plateau”. It causes muscle contraction to last 3 to 15 times longer in cardiac muscle than in skeletal one. NOTE: membrane of ventricular cell remains depolarized about 300 msec (unlike skeletal muscle). This prolonged phase of depolarization is called “plateau”. It causes muscle contraction to last 3 to 15 times longer in cardiac muscle than in skeletal one.

9. Three types of ion channels form the AP of cardiac muscle: (1) fast sodium channels (that can be fast activated and fast inactivated); (1) fast sodium channels (that can be fast activated and fast inactivated); (2) slow calcium channels (that can be slow activated and slow inactivated); they are called also calcium- sodium channels because of permeability for sodium ions; this type of ion channel is absent in skeletal muscle; (2) slow calcium channels (that can be slow activated and slow inactivated); they are called also calcium- sodium channels because of permeability for sodium ions; this type of ion channel is absent in skeletal muscle; (3)slow potassium channels (that have not inactivated mechanism). (3)slow potassium channels (that have not inactivated mechanism).

10. 1. Firstly fast Na-channels become opened and inward Na-current provokes depolarization of the cell membrane and overshoot. Then these channels become inactivated and Na-current ceases. 1. Firstly fast Na-channels become opened and inward Na-current provokes depolarization of the cell membrane and overshoot. Then these channels become inactivated and Na-current ceases.

11. 2. Then slow Ca-channels become opened and inward Ca-current (+ Na-current) continue to depolarize the cell membrane (phase “plateau”). During depolarization the permeability of the cardiac muscle membrane for K+ decreases (5-fold) owing the excess of Ca-influx (This prevents early return of the potential to its resting level). Then Ca- channels become inactivated and Ca-current ceases. 2. Then slow Ca-channels become opened and inward Ca-current (+ Na-current) continue to depolarize the cell membrane (phase “plateau”). During depolarization the permeability of the cardiac muscle membrane for K+ decreases (5-fold) owing the excess of Ca-influx (This prevents early return of the potential to its resting level). Then Ca- channels become inactivated and Ca-current ceases.

12. 3. At last, slow potential-depended K- channels become opened and outward K- current provokes fast repolarization (to resting level –90 mv). 3. At last, slow potential-depended K- channels become opened and outward K- current provokes fast repolarization (to resting level –90 mv).

13. Refractory period of cardiac muscle During phase plateau fast Na-channels remain inactivated and prolonged refractory period is present (about 300 msec). Duration of refractory period is equal duration of systole. Therefore, cardiac muscle cannot contract in form tetanus but it can contract only in form single contraction (unlike skeletal muscle).

14. VELOCITY OF CONDUCTION in cardiac muscle (atrial and ventricular) is about 0.3-0.5 m/s (only 1/250 the velocity in very large nerve fibers and 1/10 the velocity in skeletal muscle). VELOCITY OF CONDUCTION in cardiac muscle (atrial and ventricular) is about 0.3-0.5 m/s (only 1/250 the velocity in very large nerve fibers and 1/10 the velocity in skeletal muscle). The velocity of conduction in the different parts of specialized conductive system varies from 0.02 to 4 m/s. The velocity of conduction in the different parts of specialized conductive system varies from 0.02 to 4 m/s.

15. EXCITATION-CONTRACTION COUPLING mechanism is the same as that for skeletal muscle. There are transverse tubules of the cell membrane (very developed) and longitudinal tubules of the sarcoplasmic reticulum (much less developed) in the cardiac muscle cell. So the strength of contraction of cardiac muscle depends to a great extant on the concentration of Ca in the extracellular fluids (owing inward Ca- current during phase plateau when the T- tubule action potential occurs). EXCITATION-CONTRACTION COUPLING mechanism is the same as that for skeletal muscle. There are transverse tubules of the cell membrane (very developed) and longitudinal tubules of the sarcoplasmic reticulum (much less developed) in the cardiac muscle cell. So the strength of contraction of cardiac muscle depends to a great extant on the concentration of Ca in the extracellular fluids (owing inward Ca- current during phase plateau when the T- tubule action potential occurs).

16. SPECIAL PROPERTIES OF CARDIAC MUSCLE excitationconductioncontraction Phase plateau Functional syncytium cells are electrically connected) connected) only single contraction- Tetanus is impossible Prolonged refractory period Contraction principle “all or none”

17. THE CARDIAC CYCLE period from beginning of one heart beat to the beginning of the next one (about 0.8 sec). Period of contraction is called systole and period of relaxation is called diastole (during which the heart fills with blood). Period of contraction is called systole and period of relaxation is called diastole (during which the heart fills with blood). Because atria contract ahead ventricles there are tree basic phases in cardiac cycle: Because atria contract ahead ventricles there are tree basic phases in cardiac cycle: (1) systole of atria (0.1 sec) (1) systole of atria (0.1 sec) (2) systole of ventricles (0.3 sec) (2) systole of ventricles (0.3 sec) (3) common diastole (common pause) (0.4 sec) (3) common diastole (common pause) (0.4 sec)

19. In summary, the systole of the ventricle can be subdivided into the following phases: In summary, the systole of the ventricle can be subdivided into the following phases: 1. Isovolumetric contraction 0.05 s 2. Rapid ejection 0.10 s 3. Reduced ejection 0.15 s Total 0.3 s The subdivisions of ventricular diastole are: 1. Prodiastole 0.04 s 1. Prodiastole 0.04 s 2. Isovolumetric relaxation 0.06 s 2. Isovolumetric relaxation 0.06 s 3. First rapid filling phase 0.10 s 3. First rapid filling phase 0.10 s 4. Diastasis 0.20 s 4. Diastasis 0.20 s 5. Last rapid filling phase 0.10 s 5. Last rapid filling phase 0.10 s Total about 0.5 N.B Please note that diastasis strongly depends on heart rate

21. Phases and events of the cardiac cycle P wave atrial depolarization & contraction fills the ventricles cuspid valves open while valves of vena cava and pulmonary veins are closed QRS complex atrial repolarization and relaxation & simultaneous ventricular depolarization and contraction empties the ventricles cuspid valves are closed while semilunar valves are open T wave ventricular repolarization and relaxation heart relaxes cuspid and semilunar valves are closed pause myocardium at rest atria fill after a pause of some length valves of vena cava and pulmonary veins open so atria can fill

22. Cardiac Cycle (Pressure within the chambers of the heart rises and falls) Three phases: 1. Ventricular Filling (SYSTOLE OF ATRIA) -heart in total relaxation, mid-to-late diastole -pressure in heart is low, blood returning to heart -rapid ventricular filling (70% of ventricle filling), blood flows -passively into atrium through open AV valves into ventricles -AV valve flaps drift upward to closed position -atriole systole, atrial pressure rises, propels blood into resting ventricles -ventricles now contain the maximum volume of blood called the end-diastolic volume (EDV)

23. 2. Ventricular Systole blood is pushed up against AV valves, forcing them shut blood is pushed up against AV valves, forcing them shut All four valves closed (isovolumetric contraction) All four valves closed (isovolumetric contraction) Pressure rises Pressure rises Semilunar valves open Semilunar valves open Ventricular ejection occurs Ventricular ejection occurs Ventricles start to relax, semilunar valves close Ventricles start to relax, semilunar valves close Blood remaining - end systolic volume (ESV) Blood remaining - end systolic volume (ESV)

24. 3. Relaxation/ Common diastole(Quiescent) Period (from T wave to P wave) 3. Relaxation/ Common diastole(Quiescent) Period (from T wave to P wave) Ventricles start to relax, all four chambers in diastole Ventricles start to relax, all four chambers in diastole Pressure within chambers drops, blood starts to flow from pulmonary trunk and aorta toward ventricles Pressure within chambers drops, blood starts to flow from pulmonary trunk and aorta toward ventricles Blood becomes trapped in semilunar cusps, valves close Blood becomes trapped in semilunar cusps, valves close Rebound of blood closed cusps (dicrotic wave on aortic pressure curve) Rebound of blood closed cusps (dicrotic wave on aortic pressure curve)

25. Isovolumetric relaxation occurs --> interval when ventricular blood volume does not change because both semilunar and atrioventricular valves are closed Isovolumetric relaxation occurs --> interval when ventricular blood volume does not change because both semilunar and atrioventricular valves are closed As ventricles relax, space inside expands, and pressure falls As ventricles relax, space inside expands, and pressure falls When ventricular pressure drops below atrial pressure, atrioventricular valves open and ventricular filling begins When ventricular pressure drops below atrial pressure, atrioventricular valves open and ventricular filling begins NOTE: CARDIAC OUTPUT = HR X SV. Stroke volume is equal to the difference between EDV and ESV. At rest CO = HR (75 beats/min) X SV (70 ml/beat) = 5250 ml/min NOTE: CARDIAC OUTPUT = HR X SV. Stroke volume is equal to the difference between EDV and ESV. At rest CO = HR (75 beats/min) X SV (70 ml/beat) = 5250 ml/min

27. End-diastolic volume (EDV) - The typical volume of blood, approximately 120-130 mL, found in the ventricles after they are filled by atrial contraction during ventricular diastole (before the ventricles contract); the actual volume will depend on venous return of blood to the heart. End-systolic volume (ESV) - The residual volume of blood, approximately 50-60 mL, found in the ventricles after systole (when the ventricles have contracted); the volume varies in response to activity levels and to disease states. Venous return - The amount of blood delivered to the atria by the veins of the pulmonary and systemic circulations; venous return is influenced by blood pressure, gravity, blood volume, activity levels and by disease states.

30. The maximum pressure occurs after ventricular systole and is known as the systolic pressure. When the blood pressure in the aorta exceeds that in the ventricle, the aortic valve closes; this accounts for the dicrotic notch.

32. Summary of the cardiac cycle I. SYSTOLE OF ATRIA Atria are primer pumps. Atria are primer pumps. During ventricular systole, large amount of blood accumulates in the atria (because A-V valves are closed). During ventricular systole, large amount of blood accumulates in the atria (because A-V valves are closed). At the beginning of ventricular diastole (when pressure in the ventricles fall and A-V valves open) blood enter rapidly into the ventricles. At the beginning of ventricular diastole (when pressure in the ventricles fall and A-V valves open) blood enter rapidly into the ventricles. About 75% of the blood flows directly through the atria into ventricles before the atria contraction (passive filling of ventricles). Atria contraction causes an additional 25% filling of the ventricles (active filling of ventricles). Atria pressure rises 6 to 8 mm Hg during their contraction. About 75% of the blood flows directly through the atria into ventricles before the atria contraction (passive filling of ventricles). Atria contraction causes an additional 25% filling of the ventricles (active filling of ventricles). Atria pressure rises 6 to 8 mm Hg during their contraction.

33. II. SYSTOLE OF VENTRICLES (a) period of isovolumic (isometric) contraction After ventricular contraction begins the ventricular pressure abruptly rises and A-V valves close. Semilunar valves of aorta and pulmonary artery are closed too. Volume of blood remains constant in the ventricles. Volume of blood remains constant in the ventricles. (b) period of ejection When the ventricular pressure rises above diastolic pressure in the vessels (70-80 mm Hg in the left ventricle and 8-10 mm in the right one) semilunar valves open. Blood begins enter vessels: first third of the period of ejection – 70% of blood (period of rapid ejection) and remained 2/3 of the period – 30% of blood (period of slow ejection).

34. III. COMMON DIASTOLE Relaxation of ventricles begin suddenly, intraventricular pressure falls rapidly, semilunar valves close, A-V valves remain closed too (period of isovolumic relaxation of the ventricles). Relaxation of ventricles begin suddenly, intraventricular pressure falls rapidly, semilunar valves close, A-V valves remain closed too (period of isovolumic relaxation of the ventricles). Then A-V valves open and filling of the ventricles begins (period of rapid filling, period of slow filling). During common pause passive filling of ventricles occurs (both atria and ventricles are relaxed). Pressure in the ventricles is about zero during this phase. Then A-V valves open and filling of the ventricles begins (period of rapid filling, period of slow filling). During common pause passive filling of ventricles occurs (both atria and ventricles are relaxed). Pressure in the ventricles is about zero during this phase.

35. FUNCTION OF THE VALVES They prevent backflow of the blood. They close and open passively (owing to gradient of pressure). They prevent backflow of the blood. They close and open passively (owing to gradient of pressure). (Contraction of sphincters prevents backflow of the blood from atria into venous vessels). (Contraction of sphincters prevents backflow of the blood from atria into venous vessels).

36. CONDUCTING SYSTEM OF THE HEART There is specialized excitatory and conductive system in the heart: There is specialized excitatory and conductive system in the heart: sinus node (sinoatrial), in which the normal rhythmical impulses are generated; sinus node (sinoatrial), in which the normal rhythmical impulses are generated; internodal pathways that conduct impulses from the sinus node to the A-V node; internodal pathways that conduct impulses from the sinus node to the A-V node; A-V node (atrioventricular node) in which impulse from the atria is delayed before passing into the ventricles; A-V node (atrioventricular node) in which impulse from the atria is delayed before passing into the ventricles; A-V bundle, which conducts impulse from the atria into the ventricles; A-V bundle, which conducts impulse from the atria into the ventricles; left and right bundles of Purkinje fibers, which conduct impulses to all parts of the ventricles. left and right bundles of Purkinje fibers, which conduct impulses to all parts of the ventricles. This system has the capability of self-excitation (so the heart can be excited and contracts automatically). This system has the capability of self-excitation (so the heart can be excited and contracts automatically).

38. SINUS NODE Each cardiac cycle is initiated by spontaneous generation of action potential in the sinus node. It is located in the wall of right atrium near the opening of the superior vena cava. Each cardiac cycle is initiated by spontaneous generation of action potential in the sinus node. It is located in the wall of right atrium near the opening of the superior vena cava. “Resting” potential of the cell of the sinus node is about -55 mv (because of low permeability for K-ions and high permeability for Na-ions at rest). At this level of negativity fast Na-channels are inactivated. Only slow Ca- channels can open (become activated) and thereby cause the AP. AP is slower, with a slow decrement. “Resting” potential of the cell of the sinus node is about -55 mv (because of low permeability for K-ions and high permeability for Na-ions at rest). At this level of negativity fast Na-channels are inactivated. Only slow Ca- channels can open (become activated) and thereby cause the AP. AP is slower, with a slow decrement. Self-excitation: At rest Na-ions outside the fibers tend to leak to the inside. ”Resting” potential gradually rises between each two heart beats. This is SDD -spontaneous diastolic depolarization. When it reaches a threshold voltage (-40 mv), the slow Ca-channels become activated and the AP is generated. Then Ca-channels are inactivated; K-ions diffuse out of the fibers and membrane potential returns at “resting” level. Then K-channels begin to close, leakage of Na-ions to the internal provokes SDD again and all cycle is repeated. Self-excitation: At rest Na-ions outside the fibers tend to leak to the inside. ”Resting” potential gradually rises between each two heart beats. This is SDD -spontaneous diastolic depolarization. When it reaches a threshold voltage (-40 mv), the slow Ca-channels become activated and the AP is generated. Then Ca-channels are inactivated; K-ions diffuse out of the fibers and membrane potential returns at “resting” level. Then K-channels begin to close, leakage of Na-ions to the internal provokes SDD again and all cycle is repeated.

39. ATRIOVENTRICULAR NODE It is located in the posterior septal wall of the right atrium. It occurs delay in impulse conduction (about 0.13 sec) It is located in the posterior septal wall of the right atrium. It occurs delay in impulse conduction (about 0.13 sec) CAUSES OF THE SLOW CONDUCTION: CAUSES OF THE SLOW CONDUCTION: (1) small sizes of the cells (1) small sizes of the cells (2) their resting potential is much less negative that causes low voltage to drive the ions (2) their resting potential is much less negative that causes low voltage to drive the ions (3) gap junctions has great resistance to the movement of the ions. (3) gap junctions has great resistance to the movement of the ions.

41. A-V BUNDLE normally occurs one-way conduction (from atria toward ventricles). [In rare instances, abnormal muscle bridge does penetrate the fibrous barrier between atria and ventricles besides at the A-V bundle. Under such conditions the cardiac impulse can re-enter the atria from the ventricles and cause serious arrhythmia]. A-V BUNDLE normally occurs one-way conduction (from atria toward ventricles). [In rare instances, abnormal muscle bridge does penetrate the fibrous barrier between atria and ventricles besides at the A-V bundle. Under such conditions the cardiac impulse can re-enter the atria from the ventricles and cause serious arrhythmia]. A-V bundle divides into left and right bundle brunches that lie beneath endocardium. The terminal Purkinje fibers penetrate about 1/3 of the way into the muscle mass. Then impulse is transmitted by the ventricular muscle fibers themselves. Direction of transmission is (a) from the apex of the ventricles toward base and (b) from the endocardium toward epicardium. A-V bundle divides into left and right bundle brunches that lie beneath endocardium. The terminal Purkinje fibers penetrate about 1/3 of the way into the muscle mass. Then impulse is transmitted by the ventricular muscle fibers themselves. Direction of transmission is (a) from the apex of the ventricles toward base and (b) from the endocardium toward epicardium.

42. PACEMAKER OF THE HEART NOTE: sinus node is the pacemaker of the heart. The normal rate of the sinus node is 70-80 times per min. (the rate of A-V node is 40-60; the rate of Purkinje fibers is between 15 and 40). NOTE: sinus node is the pacemaker of the heart. The normal rate of the sinus node is 70-80 times per min. (the rate of A-V node is 40-60; the rate of Purkinje fibers is between 15 and 40). Sinus node has a high velocity of its own depolarization and emits its impulse before A-V node can reach its own threshold for excitation. So sinus node always excites other potentially self-excitatory tissues before their self-excitation can occur. Thus sinus node controls the beat of the heart. Sinus node has a high velocity of its own depolarization and emits its impulse before A-V node can reach its own threshold for excitation. So sinus node always excites other potentially self-excitatory tissues before their self-excitation can occur. Thus sinus node controls the beat of the heart.

43. A pacemaker elsewhere than the sinus node is called an ectopic pacemaker (abnormal). A pacemaker elsewhere than the sinus node is called an ectopic pacemaker (abnormal). When A-V block occurs the atria continue to beat at the normal rate of rhythm of the sinus node, while a new pacemaker develops in the Purkinje system of the ventricles and drives the ventricular muscle at a new rate between 15 and 40 beats per min. When A-V block occurs the atria continue to beat at the normal rate of rhythm of the sinus node, while a new pacemaker develops in the Purkinje system of the ventricles and drives the ventricular muscle at a new rate between 15 and 40 beats per min. NOTE: effective pumping by the two ventricular chambers requires synchronous type of their contraction. Slow transmission provokes much of ventricular mass to contract before contraction of the remainder. Pumping effectiveness of the ventricles is decrease 20-30%. NOTE: effective pumping by the two ventricular chambers requires synchronous type of their contraction. Slow transmission provokes much of ventricular mass to contract before contraction of the remainder. Pumping effectiveness of the ventricles is decrease 20-30%.

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