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Home , Coronary circulation, Coronary sulcus

Physiology of Unit-4 (ZOOA-CC4-9-TH)

Coronary Circulation:

The heart muscle, like every other organ or tissue in your body, needs oxygen-rich to survive. Blood is supplied to the heart by its own vascular system, called . The (the main blood supplier to the body) branches off into two main coronary blood vessels (also called ). These branch off into smaller arteries, which supply oxygen-rich blood to the entire heart muscle. The right coronary supplies blood mainly to the right side of the heart. The right side of the heart is smaller because it pumps blood only to the lungs. The left coronary artery, which branches into the left anterior descending artery and the circumflex artery, supplies blood to the left side of the heart. The left side of the heart is larger and more muscular because it pumps blood to the rest of the body.

Coronary circulation is the circulation of blood in the blood vessels that supply the heart muscle (myocardium).

Coronary arteries supply oxygenated blood to the heart muscle, and cardiac drain away the blood once it has been deoxygenated. Because the rest of the body, and most especially the brain, needs a steady supply of oxygenated blood that is free of all but the slightest interruptions, the heart is required to function continuously. Therefore its circulation is of major importance not only to its own tissues but to the entire body and even the level of consciousness of the brain from moment to moment. Interruptions of coronary circulation quickly cause heart attacks (myocardial infarctions), in which the heart muscle is damaged by oxygen starvation. Such interruptions are usually caused by coronary linked to , and sometimes to from other causes like obstruction in blood flow through vessels.

Structure: Coronary arteries supply blood to the myocardium and other components of the heart. Two coronary arteries originate from the left side of the heart at the beginning (root) left . There are three aortic sinuses (dilations) in the wall of the aorta just superior to the aortic semilunar valve. Two of these, the left posterior and anterior aortic sinus, give rise to the left and right coronary arteries, respectively. The third sinus, the right posterior aortic sinus, typically does not give rise to a vessel. Coronary vessel branches that remain on the surface of the heart and follow the sulci of the heart are called epicardial coronary arteries. The left coronary artery distributes blood to the left side of the heart, the left and ventricle, and the . The circumflex artery arises from the left coronary artery and follows the to the left. Eventually, it will fuse with the small branches of the right coronary artery. The larger anterior interventricular artery, also known as the left anterior descending artery (LAD), is the second major branch arising from the left coronary artery. It follows the anterior interventricular sulcus around the pulmonary trunk. Along the way it gives rise to numerous smaller branches that interconnect with the branches of the posterior interventricular artery, forming anastomoses. An is an area where vessels unite to form interconnections that normally allow blood to circulate to a region even if there may be partial blockage in another branch. The anastomoses in the heart are very small. Therefore, this ability is somewhat restricted in the heart so a coronary artery blockage often results in causing death of the cells supplied by the particular vessel. The right coronary artery proceeds along the coronary sulcus and distributes blood to the right atrium, portions of both ventricles, and the heart conduction system. Normally, one or more marginal arteries arise from the right coronary artery inferior to the right atrium. The marginal arteries supply blood to the superficial portions of the right ventricle. On the posterior surface of the heart, the right coronary artery gives rise to the posterior interventricular artery, also known as the posterior descending artery. It runs along the posterior portion of the interventricular sulcus toward the apex of the heart, giving rise to branches that supply the interventricular septum and portions of both ventricles.

Anastomoses: There are some anastomoses between branches of the two coronary arteries. However the coronary arteries are functionally end arteries and so these meetings are referred to as potential anastomoses, which lack function, as opposed to true anastomoses like that in the palm of the hand. This is because blockage of one coronary artery generally results in death of the heart tissue due to lack of sufficient blood supply from the other branch. When two arteries or their branches join, the area of the myocardium receives dual blood supply. These junctions are called anastomoses. If one coronary artery is obstructed by an , the second artery is still able to supply oxygenated blood to the myocardium. However, this can only occur if the atheroma progresses slowly, giving the anastomoses a chance to proliferate. Under the most common configuration of coronary arteries, there are three areas of anastomoses. Small branches of the LAD (left anterior descending/anterior interventricular) branch of the left coronary join with branches of the posterior interventricular branch of the right coronary in the interventricular sulcus (groove). More superiorly, there is an anastomosis between the circumflex artery (a branch of the left coronary artery) and the right coronary artery in the atrioventricular groove. There is also an anastomosis between the septal branches of the two coronary arteries in the interventricular septum. The photograph shows area of heart supplied by the right and the left coronary arteries.

Variation The left and right coronary arteries occasionally arise by a common trunk, or their number may be increased to three; the additional branch being the posterior coronary artery (which is smaller in size). In rare cases, a person will have the third coronary artery run around the root of the aorta. Occasionally, a coronary artery will exist as a double structure (i.e. there are two arteries, parallel to each other, where ordinarily there would be one).

Coronary arteries supply blood to the heart muscle. Like all other tissues in the body, the heart muscle needs oxygen-rich blood to function. Also, oxygen-depleted blood must be carried away. The coronary arteries wrap around the outside of the heart. Small branches dive into the heart muscle to bring it blood.

What are the different coronary arteries?

The 2 main coronary arteries are the left main and right coronary arteries.  Left main coronary artery (LMCA). The left main coronary artery supplies blood to the left side of the heart muscle (the left ventricle and left atrium). The left main coronary divides into branches:

 The left anterior descending artery branches off the left coronary artery and supplies blood to the front of the left side of the heart.  The circumflex artery branches off the left coronary artery and encircles the heart muscle. This artery supplies blood to the outer side and back of the heart.

 Right coronary artery (RCA). The right coronary artery supplies blood to the right ventricle, the right atrium, and the SA (sinoatrial) and AV (atrioventricular) nodes, which regulate the heart rhythm. The right coronary artery divides into smaller branches, including the right posterior descending artery and the acute marginal artery. Together with the left anterior descending artery, the right coronary artery helps supply blood to the middle or septum of the heart.

Smaller branches of the coronary arteries include: obtuse marginal (OM), septal perforator (SP), and diagonals.

Why are the coronary arteries important?

Since coronary arteries deliver blood to the heart muscle, any coronary artery disorder or disease can have serious implications by reducing the flow of oxygen and nutrients to the heart muscle. This can lead to a heart attack and possibly death. (a buildup of plaque in the inner lining of an artery causing it to narrow or become blocked) is the most common cause of heart disease.

The heart receives its own supply of blood from the coronary arteries. Two major coronary arteries branch off from the aorta near the point where the aorta and the left ventricle meet. These arteries and their branches supply all parts of the heart muscle with blood. Left Main Coronary Artery (also called the left main trunk)

The left main coronary artery branches into:

 Circumflex artery  Left Anterior Descending artery (LAD)

The left coronary arteries supply:

 Circumflex artery - supplies blood to the left atrium, side and back of the left ventricle  Left Anterior Descending artery (LAD) - supplies the front and bottom of the left ventricle and the front of the septum

Right Coronary Artery (RCA)

The right coronary artery branches into:

 Right marginal artery  Posterior descending artery

The right coronary artery supplies:

 Right atrium  Right ventricle  Bottom portion of both ventricles and back of the septum

The main portion of the right coronary artery provides blood to the right side of the heart, which pumps blood to the lungs. The rest of the right coronary artery and its main branch, the posterior descending artery, together with the branches of the circumflex artery, run across the surface of the heart's underside, supplying the bottom portion of the left ventricle and back of the septum.

The major vessels of the coronary circulation are the left main coronary that divides into left anterior descending and circumflex branches, and the right main coronary artery. The left and right coronary arteries originate at the base of the aorta from openings called the coronary ostia located behind the leaflets.

The left and right coronary arteries and their branches lie on the surface of the heart, and therefore are sometimes referred to as the epicardial coronary vessels. These vessels distribute blood flow to different regions of the heart muscle. When the vessels are not diseased, they have a low vascular resistance relative to their more distal and smaller branches that comprise the microvascular network. As in all vascular beds, it is the small arteries and arterioles in the microcirculation that are the primary sites of vascular resistance, and therefore the primary site for regulation of blood flow. The arterioles branch into numerous capillaries that lie adjacent to the cardiac myocytes. A high capillary-to- cardiomyocyte ratio and short diffusion distances ensure adequate oxygen delivery to the myocytes and removal of metabolic waste + products from the cells (e.g., CO2 and H ). Capillary blood flow enters venules that join together to form cardiac veins that drain into the coronary sinus located on the posterior side of the heart, which drains into the right atrium. There are also anterior cardiac veins and thesbesian veins drain directly into the cardiac chambers.

The following summarizes important features of coronary blood flow:

 Flow is tightly coupled to oxygen demand. This is necessary because the heart has a very high basal oxygen consumption (8-10 ml O2/min/100g) and the highest A- VO2 difference of a major organ (10-13 ml/100 ml). In non- diseased coronary vessels, whenever cardiac activity and oxygen consumption increases there is an increase in coronary blood flow (active hyperemia) that is nearly proportionate to the increase in oxygen consumption.  Good autoregulation between 60 and 200 mmHg perfusion pressure helps to maintain normal coronary blood flow whenever coronary perfusion pressure changes due to changes in aortic pressure.  Adenosine is an important mediator of active hyperemia and autoregulation. It serves as a metabolic coupler between oxygen consumption and coronary blood flow. Nitric oxide is also an important regulator of coronary blood flow.  Activation of sympathetic nerves innervating the coronary vasculature causes only transient vasoconstriction mediated by α1-adrenoceptors. This brief (and small) vasoconstrictor response is followed by caused by enhanced production of vasodilator metabolites (active hyperemia) due to increased mechanical and metabolic activity of the heart resulting from β1-adrenoceptor activation of the myocardium. Therefore, sympathetic activation to the heart results in coronary vasodilation and increased coronary flow due to increased metabolic activity (increased heart rate, contractility) despite direct vasoconstrictor effects of sympathetic activation on the coronaries. This is termed "functional sympatholysis."  Parasympathetic stimulation of the heart (i.e., vagal nerve activation) elicits modest coronary vasodilation (due to the direct effects of released acetylcholine on the coronaries). However, if parasympathetic activation of the heart results in a significant decrease in myocardial oxygen demand due to a reduction in heart rate, then intrinsic metabolic mechanisms will increase coronary vascular resistance by constricting the vessels.  Progressive ischemic coronary artery disease results in the growth of new vessels (termed angiogenesis) and collateralization within the myocardium. Collateralization increases myocardial blood supply by increasing the number of parallel vessels, thereby reducing vascular resistance within the myocardium.  Extravascular compression (shown to the right) during markedly affects coronary flow; therefore, most of the coronary flow occurs during . Because of extravascular compression, the is more susceptible to ischemia especially at lower perfusion pressures. Furthermore, with tachycardia there is relatively less time available for coronary flow during diastole to occur – this is particularly significant in patients with coronary artery disease where coronary flow reserve (maximal flow capacity) is reduced.

In the presence of coronary artery disease, coronary blood flow may be reduced. This will increase oxygen extraction from the coronary blood and decrease the venous oxygen content. This leads to tissue and . If the lack of blood flow is due to a fixed stenotic lesion in the coronary artery (because of atherosclerosis), blood flow can be improved within that vessel by 1) placing a stent within the vessel to expand the lumen, 2) using an intracoronary balloon to stretch the vessel open, or 3) bypassing the diseased vessel with a vascular graft. If the insufficient blood flow is caused by a blood clot (thrombosis), a thrombolytic drug that dissolves clots may be administered. Anti-platelet drugs and aspirin are commonly used to prevent the reoccurrence of clots. If the reduced flow is due to coronary vasospasm, then coronary vasodilators can be given (e.g., nitrodilators, calcium-channel blockers) to reverse and prevent vasospasm.

Cardiac Veins

Blood travels from the subendocardium into the thebesian veins, which are small tributaries running throughout the myocardium. These in turn drain into larger veins that empty into the coronary sinus. The coronary sinus is the main of the heart, located on the posterior surface in the coronary sulcus, which runs between the left atrium and left ventricle. The sinus drains into the right atrium. Within the right atrium, the opening of the coronary sinus is located between the right atrioventricular orifice and the inferior vena cava orifice.

There are five tributaries which drain into the coronary sinus:

 The great cardiac vein is the main tributary. It originates at the apex of the heart and follows the anterior interventricular groove into the coronary sulcus and around the left side of the heart to join the coronary sinus.

 The is also located on the anterior surface of the heart. This passes around the right side of the heart to join the coronary sinus.

 Another vein which drains the right side of the heart is the . It is located on the posterior surface of the heart.

The final 2 cardiac veins are also on the posterior surface of the heart:

 On the left posterior side is the left marginal vein.

 In the centre is the left posterior ventricular vein which runs along the posterior interventricular sulcus to join the coronary sinus.

Structure and working of conducting myocardial fibres :

The conducting system of the heart consists of cells and conducting fibers (not nervous tissue) that are specialized for initiating impulses and conducting them rapidly through the heart (see the image below). They initiate the normal cardiac cycle and coordinate the contractions of cardiac chambers. Both atria contract together, as do the ventricles, but atrial contraction occurs first. The conducting system provides the heart its automatic rhythmic beat. For the heart to pump efficiently and the systemic and pulmonary circulations to operate in synchrony, the events in the cardiac cycle must be coordinated

The cardiac conduction system is a collection of nodes and specialised conduction cells that initiate and co-ordinate contraction of the heart muscle. It consists of:

 Atrioventricular bundle ()  Purkinje fibres

Overview of Heart Conduction

The sequence of electrical events during one full contraction of the heart muscle:

 An excitation signal (an action potential) is created by the sinoatrial (SA) node.  The wave of excitation spreads across the atria, causing them to contract.  Upon reaching the atrioventricular (AV) node, the signal is delayed.  It is then conducted into the bundle of His, down the interventricular septum.  The Bundle of His and the Purkinje fibres spread the wave impulses along the ventricles, causing them to contract.

Components of the Cardiac Conduction System Sinoatrial Node

The Sinoatrial (SA) node is a collection of specialised cells (pacemaker cells), and is located in the upper wall of the right atrium, at the junction where the enters.

These pacemaker cells can spontaneously generate electrical impulses. The wave of excitation created by the SA node spreads via gap junctions across both atria, resulting in atrial contraction (atrial systole) – with blood moving from the atria into the ventricles.

The rate at which the SA node generates impulses is influenced by the autonomic nervous system:

 Sympathetic nervous system – increases firing rate of the SA node, and thus increases heart rate.  Parasympathetic nervous system – decreases firing rate of the SA node, and thus decreases heart rate.

Atrioventricular Node

After the electrical impulses spread across the atria, they converge at the atrioventricular node – located within the atrioventricular septum, near the opening of the coronary sinus.

The AV node acts to delay the impulses by approximately 120ms, to ensure the atria have enough time to fully eject blood into the ventricles before ventricular systole.

The wave of excitation then passes from the atrioventricular node into the atrioventricular bundle.

Atrioventricular Bundle

The atrioventricular bundle (bundle of His) is a continuation of the specialised tissue of the AV node, and serves to transmit the electrical impulse from the AV node to the Purkinje fibres of the ventricles.

It descends down the membranous part of the interventricular septum, before dividing into two main bundles:

 Right bundle branch – conducts the impulse to the Purkinje fibres of the right ventricle  Left bundle branch – conducts the impulse to the Purkinje fibres of the left ventricle.

Purkinje Fibres

The Purkinje fibres (sub-endocardial plexus of conduction cells) are a network of specialised cells. They are abundant with glycogen and have extensive gap junctions.

These cells are located in the subendocardial surface of the ventricular walls, and are able to rapidly transmit cardiac action potentials from the atrioventricular bundle to the myocardium of the ventricles. This rapid conduction allows coordinated ventricular contraction (ventricular systole) and blood is moved from the right and left ventricles to the and aorta respectively.

Conduction system of the heart: The cardiac conduction system is a network of specialized cardiac muscle cells that initiate and transmit the electrical impulses responsible for the coordinated contractions of each cardiac cycle. These special cells are able to generate an action potential on their own (self-excitation) and pass it on to other nearby cells (conduction), including cardiomyocytes.

The parts of the heart conduction system can be divided into those that generate action potentials (nodal tissue) and those that conduct them (conducting fibers). Although all parts have the ability to generate action potentials and thus heart contractions, the sinuatrial (SA) node is the primary impulse initiator and regulator in a healthy heart. This aspect makes the SA node the physiological pacemaker of the heart. Other parts sequentially receive and conduct the impulse originating from the SA node and then pass it to myocardial cells. Upon stimulation by the action potential, myocardial cells contract synchronously, resulting in a heartbeat. The propagation of electrical impulses and synchronous contraction of cardiomyocytes is facilitated by the presence of intercalated discs and gap junctions.

Sinoatrial node

The sinuatrial node (SA node) is a flat, elliptical collection of specialized nodal tissue with dimensions of up to 25 millimeters (mm) in length. The node is nestled in the superior posterolateral wall of the right atrium near the opening of the superior vena cava which is indicated by the sulcus terminalis (the junction of the venous sinus and the right atrium proper). Here it lies in the subepicardiac layer of the heart, often covered by a relatively thin pad. Centrally, the SA node is populated with pale-staining cells known as (P) cells. They are circumferentially arranged around the arterial supply of the node (the SA nodal branch of the coronary artery). Histologically, P cells contain a relatively large, central nucleus but a scant amount of other organelles (likely the cause of the pale staining). Unlike the surrounding cardiomyocytes, P cells have very few cytoplasmic myofibrils and no sarcotubular apparatus. The population of P cells begins to decrease towards the periphery of the SA node, where other transition cells become more apparent. These slender, fusiform cells resemble a crossover between the aforementioned P cells and typical cardiomyocytes. These transition cells form bridges between P cells and surrounding atrial cells.

The SA node receives its blood supply from the sinuatrial nodal branch of the coronary artery. In about 60% of individuals, this artery is a branch of the right coronary artery (therefore arising from the left coronary artery in the other 40%). There are numerous autonomic ganglion cells bordering the SA node anteriorly and posteriorly. However, none of these ganglia appear to terminate on the cardiac pacemaker cells. Instead, the P cells contain both cholinergic and adrenergic receptors to respond to the neurotransmitters released by the surrounding autonomic ganglion cells.

Internodal conduction pathway

The internodal conduction pathways are a part of the intra-atrial conduction network initially described by Thomas N. James in 1963. Not only do these pathways travel within the right atrium, but they also form direct points of communication between the sinoatrial and atrioventricular nodes. The internodal conduction pathway is divided into anterior, middle and posterior branches.

The anterior internodal pathway originates from the anterior margin of the SA node. It continues anteriorly, coursing around the superior vena cava where it gives off Bachmann’s bundle. The anterior internodal band continues anteroinferiorly toward the atrioventricular (AV) node where it enters the node by way of its superior margin.

The middle internodal pathway arises from the posterosuperior margin of the SA node. It continues behind the superior vena cava toward the border of the . The pathway turns caudally in the interatrial septum to enter the AV node through its superior margin.

Finally, the posterior internodal pathway emerges from the posterior margin of the sinus node. It takes a posterior course around the superior vena cava and continues across the crista terminalis toward the Eustachian ridge (valve of the inferior vena cava). The pathway then enters the interatrial septum (above the point of the coronary sinus) where it enters the AV node through its posterior surface.

These conduction pathways transmit the action potential slightly faster than the surrounding cardiomyocytes. They contain the Purkinje-like (myofibril-poor) cells,which ensures that the action potential arrives at the AV node at an appropriate time. The blood supply of these pathways is similar to the blood supply of the right atrium – the circumflex branch of the left coronary artery.

Interatrial conduction pathway

The interatrial conduction pathway, also called Bachmann’s bundle, refers to a preferential pathway of specialized cardiomyocytes that facilitate the conduction of impulses between the atria. The pathway branches from the anterior internodal pathway at the level of the superior vena cava. The Bachmann’s bundle crosses the interatrial groove (an external landmark of the interatrial septum) and passes over the limbus of the . A pad of fatty tissue separates the Bachmann’s bundle from the limbus. The pathway bifurcates into right and left branches that travel toward the right and left atrial auricles, respectively. The right branch can be further divided into superior and inferior arms. The superior arm originates at the external junction of the superior vena cava and the atrium (near the location of the SA node). The inferior arm emerges in the vestibule of the right atrium. The left branch provides some structural support to the anterior atrial wall and continues to wrap around the left atrial auricle. Proximally, the superior part of the left branch passes in front of the openings of the left pulmonary veins. The inferior part continues caudally to the vestibule of the left atrium.

From a histological perspective, the interatrial conduction pathway is a series of parallel strands of myocardium traveling in the subepicardiac layer. The myocytes within Bachmann’s bundle are encased in thin septa made of tightly packed collagen fibrils. This uninterrupted sheath also forms inter-septal connections (the function of which is not yet clear). There are five identified cell types found within the interatrial pathway. These are:

 Myofibril-rich cells – which are the same as regular cardiomyocytes.  Myofibril-poor cells – resemble Purkinje cells; are numerous in the pathway.  P cells – like those described in the sinuatrial node.  Slender transitional cells – short and narrow.  Broad transitional cells – longer and wider than slender transitional cells. The presence of these specialized cells facilitates rapid conduction of the action potential across the left atrium, minimizing the delay in depolarization between the atria. Bachmann’s bundle receives its blood supply from the sinuatrial nodal branch of the coronary artery. Have you gotten into that study groove? Keep pushing while you have the momentum and check out these articles, quizzes and video for added insight into heart , histology and function.

Atrioventricular node

There is another specialized structure in the heart, similar to the SA node described earlier, which also helps with the conduction of impulses. It is known as the atrioventricular node (AV node) and is often called the secondary pacemaker of the heart. Under normal circumstances, it functions as a conduit of electrical activity from the SA node to the ventricles of the heart. It is the only pathway by which the action potential can cross from the atria to the ventricles; as the atrioventricular septum is made of a cartilaginous structure that is unable to conduct electrical impulses. The AV node is smaller than the SA node and is located in the posteroinferior part of the interatrial septum. Specifically, the node rests in the triangle of the atrioventricular node (triangle of Koch or Koch’s triangle). This triangle is limited by the coronary sinus (basally), the septal leaflet of the (inferiorly) and the tendon of inferior pyramidal space (tendon of valve of inferior vena cava or tendon of Todaro) (superiorly).

The hemi-oval-shaped node occupies the subendocardiac layer within Koch’s triangle. The base of the node also extends into the atrial muscle. The apex of the node extends anteroinferiorly. It passes through the fibrous to form the initial part of the atrioventricular (AV) bundle (of His). The histological make-up of the AV node is relatively similar to that in the SA node. The chief differences are that there are fewer P cells and more transition cells compared to what is observed in the SA node. The AV node receives arterial blood from the atrioventricular nodal branch. This arises from the inferior interventricular branch of the right coronary artery in 80% of individuals. In the remaining 20% of individuals, the atrioventricular nodal branch stems from the circumflex branch of the left coronary artery. There is also a notable amount of autonomic ganglion cells surrounding the AV node (as observed in the SA node). However, none of these actually form synapses with the AV node. Like the SA node cells, the AV node cells also have adrenergic and cholinergic receptors in order to respond to autonomic input.

Bundle of His

The atrioventricular (AV) bundle (of His) is the initial segment of the AV node that penetrates through the fibrous trigone into the membranous part of the interventricular septum. On transverse section at the level of the fibrous body, the AV bundle may appear oval, quadrangular or triangular. A unique and important feature of the AV bundle is that it only allows the ‘forward’ movement of action potentials. Therefore, the retrograde transmission of electrical impulses from the ventricles to the atria is not allowed in a normal functioning heart. The AV bundle is supplied by the anterior and inferior interventricular branches of the coronary arteries. Right and left

As the node moves from the membranous to the muscular interventricular septum, it bifurcates into right and left bundles. The right bundle branch, emerges from the AV bundle in the membranous interventricular septum. It is a round group of narrow fascicles that travels in the myocardium before moving superficially to the subendocardiac layer space. It travels to the right side of the interventricular septum where it gives of branches to the ventricular walls before going on toward the ventricular apex. Here, it enters the septomarginal (septomarginal band) before reaching the anterior papillary muscles. The terminal arborization of the right branch supplies the and recurs to supply the rest of the ventricular wall.

The left bundle branch or crus sinistrum (Latin) branches from the atrioventricular bundle at the start of the muscular interventricular septum. It is made up of numerous small fascicles that become flattened sheets. These fascicles occupy the left half of the muscular interventricular septum. The sheet moves to the subendocardiac space as it travels toward the ventricular apex. Here it trifurcates into posterior, septal and anterior divisions. The branches will go on to activate the anterior and posterior papillary muscles, interventricular septum and the walls of the left ventricle.

The right and left bundles are populated with subendocardial branches (Purkinje fibers). These cells can be much larger than those of the surrounding heart muscles and they function quite differently than the preceding cells in the AV node. Subendocardial branches are found throughout the entire length of both bundles in the subendocardiac layer. They extend toward the cardiac apex, then curve upward and backward through the walls of the ventricles.

The fibers have far more gap junctions than the AV nodal cells and surrounding myocytes. As a result, they are able to transmit impulses 6 times faster than ventricular muscles and 150 times faster than the AV nodal fibers. The increased number of gap junctions allow more ions to pass from one cell to the next, thus increasing the rate of conduction. Furthermore, there are fewer myofibrils in Purkinje cells, resulting in little to contraction (therefore shorter to absent refractory periods) within these cells. Consequently, the bundles can achieve almost instantaneous transmission of the action potential to the rest of the ventricle once it passes through the AV node. This compensates for the delay at the AV node and allows the ventricles to contract shortly after the atria.

Note that the main branches of the atrioventricular bundle are insulated by sheaths of connective tissue. This prevents premature excitation of adjacent cardiac tissue. Therefore, the papillary muscles will depolarize first, followed by the ventricular apex, then walls. The pattern of depolarization also goes from endocardium to epicardium, since the fibers are in the subendocardiac layer.

Physiology:

How does the SA and AV nodes work? How do the impulses travel through the heart? The simple answer to both questions is an action potential.

Sinoatrial node Cardiomyocytes have the special ability to stimulate themselves (self- excitation or automaticity). The initiation of the action potential is dependent on ion channels that allow passage of ions into and out of the cells. In the case of cardiomyocytes, they have fast-acting sodium ion (Na+), slow sodium-calcium ion (Na+-Ca2+) and slow/fast potassium ion (K+) channels (among other important channels that maintain ionic equilibrium).

This automaticity is particularly enhanced in P cells. They have a lower resting membrane potential than the surrounding cardiomyocytes and transition cells due to the following factors:

 There is a high concentration of extracellular Na+ outside the nodal fibers.  A relatively large amount of Na+ channels are already open.  There is a passive diffusion of Na+ into the P cells between heartbeats due to the ‘leaky’ sodium channels.  The passive influx of Na+ causes a slow rise in the membrane potential of the cell, bringing it progressively closer to the generation threshold of an action potential. Therefore, cardiac P cells of the SA node are more readily depolarized than other cardiac cells. The SA node is also intimately connected with the surrounding heart muscles via the internodal and interatrial conduction pathways. Consequently, the generated action potential can be rapidly transmitted to other cells. This enables the SA node to set the pace at which the heart cells will depolarize and subsequently contract, making it the pacemaker of the heart. On average, the SA node can fire between 60 to 100 beats per minute at rest.

SA nodal action potentials are divided into three phases. Phase 4 is the spontaneous depolarization (pacemaker potential) that triggers the action potential once the membrane potential reaches threshold between -40 and -30 mV). Phase 0 is the depolarization phase of the action potential. This is followed by phase 3 repolarization. Once the cell is completely repolarized at about -60 mV, the cycle is spontaneously repeated.

The changes in membrane potential during the different phases are brought about by changes in the movement of ions (principally Ca++ and K+, and to a lesser extent Na+) across the membrane through ion channels that open and close at different times during the action potential. When a channel is opened, there is increased electrical conductance (g) of specific ions through that ion channel. Closure of ion channels causes ion conductance to decrease. As ions flow through open channels, they generate electrical currents that change the membrane potential.

In the SA node, three ions are particularly important in generating the pacemaker action potential. The role of these ions in the different action potential phases are illustrated in the above figure and described below:

 At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are called "funny" currents and abbreviated as "If". These depolarizing currents cause the membrane potential to begin to spontaneously depolarize, thereby initiating Phase 4. As the membrane potential reaches about -50 mV, another type of channel opens, which increases gCa++. This channel is called transient or T-type Ca++ channel. As Ca++ enters the cell through these channels down its electrochemical gradient, the inward directed Ca++ currents further depolarize the cell. When the membrane depolarizes to about -40 mV, a second type of Ca++ channel opens, which further increases gCa++. These are the so-called long-lasting, or L-type Ca++ channels. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually between -40 and -30 mV). It should be noted that a hyperpolarized state is necessary for pacemaker channels to become activated. Without the membrane voltage becoming very negative at the end of phase 3, pacemaker channels remain inactivated, which suppresses pacemaker currents and decreases the slope of phase 4. This is one reason why cellular hypoxia, which depolarizes the cell and alters phase 3 hyperpolarization, leads to a reduction in pacemaker rate (i.e., produces bradycardia). During Phase 4 there is also a slow decline in the outward movement of K+ as the K+ channels responsible for Phase 3 continue to close. This fall in K+ conductance (gK+) contributes to the depolarizing pacemaker potential.

 Phase 0 depolarization is primarily caused by increased gCa++ through the L-type Ca++ channels that began to open toward the end of Phase 4. The "funny" currents, and Ca++ currents through the T-type Ca++ channels, decline during this phase as their respective channels close. Because the movement of Ca++ through these channels into the cell is not rapid, the rate of depolarization (slope of Phase 0) is much slower than found in other cardiac cells (e.g., Purkinje cells). +  Repolarization occurs (Phase 3) as K channels open (increased gK+) thereby increasing the outward directed, hyperpolarizing K+ currents. At the same time, the L-type Ca++ channels become inactivated and close, which decreases gCa++ and the inward depolarizing Ca++ currents. During depolarization, the membrane potential (Em) moves toward the equilibrium potential for Ca++, which is about +134 mV. During repolarization, g’Ca++ (relative Ca++ conductance) decreases and + + g’K (relative K conductance) increases, which brings Em closer toward the equilibrium potential for K+, which is about -96 mV). Therefore, the action potential in SA nodal cells is primarily dependent upon changes in Ca++ and K+ conductances.

It is important to note that action potentials described for SA nodal cells are very similar to those found in the atrioventrcular (AV) node. Therefore, action potentials in the AV node, like the SA node, are determined primarily by changes in slow inward Ca++ and K+ currents, and do not involve fast Na+ currents. AV nodal action potentials also have intrinsic pacemaker activity produced by the same ion currents as described above for SA nodal cells.

Atrioventricular node

Although the main role of the AV node is to facilitate passage of the depolarization wave to the ventricles, it also has additional functions. In the absence of a functioning SA node, the AV node has the ability to take over as the pacemaker of the heart. Recall that it also has P cells that are able to establish an (albeit slower) rhythm (40 to 60 beats per minute).

The AV node is also responsible for slowing down the passage of the electrical impulse traveling to the ventricles. This important phenomenon allows more time for the ventricles to remain quiescent and fill with blood coming from the contracting atria. But how does the AV node slow down conduction?

One key feature of the transition cells and P cells in the AV node is that they have fewer gap junctions at the intercalated discs. Consequently, there is more resistance to conduction in this part of the conduction pathway than there is in other areas.

Impulse generation and conduction :

Now let’s put all that information together and outline the cardiac conduction steps:

 The SA node generates the action potential.  The action potential passes along the internodal and interatrial conduction pathways, causing atrial systole.  The impulse arrives at the AV node and is slowed down to facilitate ventricular filling (ventricular diastole).  The impulse then passes from the AV node to the AV bundle.  It is then rapidly dispersed through the bundle branches and subendocardial tissue causing ventricular systole.  Autonomic regulation

The entire cardiac conduction system is under the influence of the autonomic pathway. Sympathetic stimulation of the conductive tissue comes from the cardiac plexus, while parasympathetic influence arises from the vagus nerve.

Activation of the sympathetic nervous system results in the release of adrenaline (epinephrine) and other adrenergic neurochemicals. They bind to beta-1 and beta-2 receptors found in both the SA and AV nodes, as well as along the supporting conduction pathways. The overall impact of the sympathetic system is an increase in the depolarization rate of the SA node. Consequently, this elevates the overall heart rate (increased chronotropy). Since these adrenergic receptors are also present on cardiomyocytes, the sympathetic drive will act on these cells, increasing the contraction force (increased inotropy). Therefore, the overall cardiac output will be increased.

On the other hand, the parasympathetic activation of muscarinic receptors at the SA and AV nodes will have the opposite effect when compared to the sympathetic system. Parasympathetic stimulation slows down SA node activation, thus reducing the heart rate. It also reduces the contractility of the cardiomyocytes, effectively reducing the cardiac output.

Cardiac cycle:

The period of timethat begins with contraction of the atria and ends with ventricular relaxation is known as the cardiac cycle. The period of contraction that the heart undergoes while it pumps blood into circulation is called systole. The period of relaxation that occurs as the chambers fill with blood is called diastole. Both the atria and ventricles undergo systole and diastole, and it is essential that these components be carefully regulated and coordinated to ensure blood is pumped efficiently to the body.

Pressures and Flow

Fluids, whether gases or liquids, are materials that flow according to pressure gradients—that is, they move from regions that are higher in pressure to regions that are lower in pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the veins, which are higher in pressure. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. Again, as you consider this flow and relate it to the conduction pathway, the elegance of the system should become apparent.

Phases of the Cardiac Cycle

At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70–80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left.

Atrial Systole and Diastole

Contraction of the atria follows depolarization, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70– 80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the “atrial kick,” contributes the remaining 20–30 percent of filling. Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole.

Ventricular Systole

Ventricular systole follows the depolarization of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to atrial contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload. Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction, also called isovolumetric contraction. In the second phase of ventricular systole, the ventricular ejection phase, the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70–80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50–60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV).

Ventricular Diastole

Ventricular relaxation, or diastole, follows repolarization of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms. During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase, also called isovolumetric ventricular relaxation phase . In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed. The cardiac cycle is complete.

A single cycle of cardiac activity can be divided into two basic phases - diastole and systole.

Diastole represents the period of time when the ventricles are relaxed (not contracting).Throughout most of this period, blood is passively flowing from the left atrium (LA) and right atrium (RA) into the left ventricle (LV) and right ventricle (RV), respectively (see figure at right). The blood flows through atrioventricular valves (mitral and tricuspid) that separate the atria from the ventricles. The RA receives venous blood from the body through the superior vena cava (SVC) and inferior vena cava (IVC). The LA receives oxygenated blood from lungs through four pulmonary veins that enter the LA. At the end of diastole, both atria contract, which propels an additional amount of blood into the ventricles.

Systole represents the time during which the left and right ventricles contract and eject blood into the aorta and pulmonary artery, respectively. During systole, the aortic and pulmonic valves open to permit ejection into the aorta and pulmonary artery. The atrioventricular valves are closed during systole, therefore no blood is entering the ventricles; however, blood continues to enter the atria though the vena cavae and pulmonary veins.

Cardiac output: For the body to function properly, the heart needs to pump blood at a sufficient rate to maintain an adequate and continuous supply of oxygen and other nutrients to the brain and other vital organs. Cardiac output is the term that describes the amount of blood your heart pumps each minute. Doctors think about cardiac output in terms of the following equation: Cardiac output = stroke volume × heart rate The stroke volume is the amount of blood your heart pumps each time it beats, and your heart rate is the number of times your heart beats per minute. What is a normal cardiac output? A healthy heart with a normal cardiac output pumps about 5 to 6 liters of blood every minute when a person is resting. When does the body need a higher cardiac output? During exercise, your body may need three or four times your normal cardiac output, because your muscles need more oxygen when you exert yourself. During exercise, your heart typically beats faster so that more blood gets out to your body. Your heart can also increase its stroke volume by pumping more forcefully or increasing the amount of blood that fills the left ventricle before it pumps. Generally speaking, your heart beats both faster and stronger to increase cardiac output during exercise. Why is maintaining cardiac output so important? Sufficient cardiac output helps keep blood pressure at the levels needed to supply oxygen-rich blood to your brain and other vital organs.