Greetings, today we want to start our discussion of the cardiovascular system. In particular we will consider the heart, the structure of the heart, and how the heart activities are coordinated by an electrical conduction system. The first thing to think about is that your heart is about the size of your fist. It sits about here in your chest. The point (apex) of the heart points down towards your feet. What we want to talk about is the conduction system of the heart. These are specialized cardiac myocytes. They do not generate any force or tension. Instead they mediate the electrical activity (control) within the heart. Secondly we will discuss the pacemaker activity. As you all know, the heart has an intrinsic beat. That's due to the pacemaker cells, this electrical conduction system. And third we will discuss how this system is regulated. You know that you can speed up your heart as you run, and you can slow your heart as you sleep. This is mediated by the autonomic nervous system. The fourth is we want to relate the activity of a single cardiac myocyte to the entire electrical activity of the whole heart. And understand how a cardiologist can view the electrical activity of the entire heart on what's known as the electrocardiogram. So, we have several things to deal with. The first is what is the structure of the heart? The structure of the heart is actually two pumps in series. We have one located on the right side. This is the side which sends blood to the lung for oxygenation. Then we have a second pump located on the left side. It receives blood from the lung, and then pumps it out to the peripheral circulatory system. We have in essence a movement, a unidirectional movement of blood through this system from the right side to the left side. In addition, the right and the left sides are divided into two compartments or two chambers. The upper is called the atrium, and the lower is the ventricle. So, we have a right atrium, and a right ventricle, a left atrium, and a left ventricle. The blood is going to move between the atria to the ventricles in a very ordered or unidirectional manner. The thing that we should notice is that the right atrium and the left atrium are separated by what's called a septum. The right ventricle and the left ventricle are also divided by what's called the septum. These septa are made up of cardiac myocytes. This means the electrical activity that's within the two chambers, that is the atria, the right and the left, and the ventricle, the right and the left, can be electrically coupled. The second thing to notice is that the atria and the ventricles are separated. They are separated at the junction, which is called the base of the heart. This junction between atria and ventricle does not consist of cardiac myocytes, but instead it's connective tissue. This effectively isolates the electrical activity of what's happening in the upper chambers that is in the atria from the electrical activity of what's happening in the lower chambers or in the ventricles. We'll come back to that thought in a few minutes. Okay, so I said to you then that we're going to have an electrical activity, which will depolarizes the cells. As we depolarize the cells then you know that in muscle, depolarization is followed by a contraction and then relaxation. Before relaxation occurs, we have to repolarize the cells. The electrical activity will always precede the contractual event. What about these electrical activities? They have to go in a unidirectional manner, because we want to have a unidirectional contraction occurring that is first in the atria and then the ventricles. This is coordinated by the electrical conduction system, or by these specialized cardiac myocytes, which are called the pacemakers. In the heart, there are several pacemakers. The first is the Sino-Atrial pacemaker, or the SA node. It is located in the right atrium, towards the upper region of the right atrium. This is a very fast pacemaker. It beats at about 60 to 100 beats per minute. The second pacemaker resides at the junction between the atrium and the ventricle on the right side. That is shown here. This is the Atrial-Ventricular node or the AV node. At the AV node, we will have a slight pause in the electrical activity that's occurring within the atria, and then the AV node will fire. It fires at about 40 to 60 beats per minute. What's unusual about this node is that everywhere else across this junction between the atria and the ventricle, the electrical activity cannot move from the upper chambers to the lower chambers. But, at the AV node, the electrical signal now will be allowed to move from the atria then down to the ventricles. So it's the gateway from the upper chamber to the lower chamber. It brings the electrical activity into the lower chambers. Within the lower chamber itself, within the septum, is the very next pacemaker. This is called the Bundle of His. This Bundle of His separates into a right and left bundle branch. These reside within the septum. So we have a splitting of the Bundle of His into a left and a right bundle branch. These fibers proceed down the septum and up the walls of the ventricles in what's called the Purkinje fibers. All pacemakers have an intrinsic beat. But here this intrinsic beat is the slowest of all. This is between 25 and 45 beats per minute. Repolarization will occur in the opposite direction. The entire event takes about 400 to 500 milliseconds. So for every beat in your heart, where you hear a lub-dub, lub-dub, then this entire conduction system is going to fire, Consequently, following the firing, there is contraction first of the atria, and then of the ventricles. Now the pacemaker potential, as you all know, has an unstable resting membrane potential. It differs from the fast action potential that we saw in the contractile myocytes, which generate tension. The pacemaker potential is called the slow pacemaker action potential, Its duration is 150 milliseconds, in contrast to what we saw with the contractal myocytes where their action potential was about 200-220 milliseconds. So itis shorter in duration. It is a pacemaker potential in that it has unstable resting membrane potential. The resting membrane potential starts at about -55 millivolts, and then slowly moves towards threshold. Threshold is minus 35 millivolts. When the membrane potential reaches minus 35 millivolts, then there is a very rapid opening of voltage gated calcium channels. This allows calcium to enter the cells. We have a depolarization of the cells. Following that, there is an opening of the voltage gated potassium channels. The voltage gated calcium channels close. With opening of the voltage gated potassium channels, there is repolarization of the cells. We return to the low resting membrane potential of a -55 millivolts. So a few things to notice. One is, is that this is slow movement from the -55 millivolts to -35 millivolts or threshold. This period is called phase 4. Phase 4 exhibits odd activities for channels. One of them is that there is a channel called the sodium funny channel. This is a voltage gated sodium channel which physiologists thought was very odd because it opened at very low voltage and then closed at very low voltage. This behavior is unlike the voltage gated sodium channel, that is active in the rapid depolarization that occurs in the contractile myocytes. So these funny channels open and close at a very low voltage. Secondly, the funny channels as they open and close, cause the membrane voltage to drift to almost toward threshold. During this period, we also open voltage gted calcium channels. Voltage gated calcium channels open and close during this period. So phase 4 is due to the opening and closing of the sodium funny channels and also the opening and closing of the voltage gated calcium channels. Once threshold is met then Phase 0 begins. And in Phase 0 now, there is a more rapid depolarization. This is due to the opening of other voltage gated calcium channels. The voltage gated calcium channels open, more calcium enters the cell. We have depolarization. The voltage gated calcium channels close. We begin Phase 3 with the opening of the voltage gated potassium channels. As potassium leaves these cells to enter into the extracellular space, then the cells repolarize. Now as you know, as you go through your day, the heart rate can change. So, as you're sitting here, your heart rate will have a basal rate of about 70 to 80 beats per minute, but if you decide that you want to go running, then your heart has to increase its cardiac output. That is you have to increase the amount of blood that's being pumped to the body to meet the oxygen demands of the skeletal muscles in your legs. To do that the heart increase its rate of firing and so of beating. This is done predominately by changing the phase four duration. By changing phase four duration in the action potential, we can more rapidly move from our basal minus 55 resting membrane potential to threshold. This is under the control of the sympathetic nervous system. The sympathetic nervous system speeds up the heart rate then by decreasing the open time of the channels. It speeds up closure of the potassium channels, the voltage-gated potassium channels of phase 3. And it changes the time for opening of the voltage-gated sodium funny channels and of our voltage-gated calcium channels. It takes less time to reach threshold. When you have a heart rate greater than 100 beats per minute, this is said to be tachycardia. Now, obviously, you need tachycardia when you're running, but then when you stop and you sit down and relax, then your heart rate will again fall to its resting membrane potential. It is not maintained at greater than 100 beats per minute. Now you also control the heart rate. That is we can slow it down as I just indicated. By slowing down the heart rate to less than 60 beats per minute, this is called bradycardia. In the daily life we have a resting heart rate between about 60 to 80 beats per minute. This is done through input from the parasympathetic nervous system. The parasympathetic nervous system acts through the muscarinic receptors which are present in the heart. It will cause a prolonged opening of the phase 3 voltage gated potassium channels. By doing that we decrease the level of hyperpolarization within the cells. We are actually further hyperpolarizing the cells. More potassium leaves these cells than under normal circumstances. Instead of starting at a minus 55 millivolts, we may be starting at a minus 65 millivolts. In addition to that, the autonomic nervous system slows the opening of the sodium funny channels and, obviously, of the voltage gated calcium channels. Consquently the slope for phase 4 then is reduced. It takes longer for pacemaker cells to reach threshold. By doing so then, it slows heart rate. So, when do we have a slowed heart rate? So, we have a slowed heart rate when we're sleeping but you can also have a slowed heart rate through training. For instance, my son went in to have his wisdom teeth taken out. When he went in to have his wisdom tooth extracted, he sat down in the office of the oral surgeon. The nurse came out and she took his heart rate. Then, she went back to the oral surgeon and said, he has a rate rate of 50 beats per minute. This is someone who's about to go in for surgery to have his wisdom teeth removed. He has a heart rate of 50 bpm. If it was I who was sitting in the chair, I would probably have a heart rate of 150, because I would be nervous. My heart rate would increase due to sympathetic drive, due to to activating the beta-1 adrenergic receptors on my heart. But, this individual, this fellow actually has heart rate of only a 50 bpm. The surgeon came out, take one look at him and he said, "okay, what do you play?" My son said, soccer. Put him under. what was that about? Simply that athletes with training, have a much higher parasympathetic tone. That is a higher parasympathetic activity on their hearts. This lowers the heart rate basal level. of beating. That is the resting membrane potential of the heart is lower, more negative. The heart rate is much slower. They have a much slower beat. In fact, Lance Armstrong, the famous bicyclist, was said to have a heart rate of about 35 beats per minutes at rest. So having a slow heart rate that is bradycardia can actually be perfectly normal in a trained individual. But in a person who has pathology in the heart, bradycardia is an indication that the heart is weak. That there's something wrong with the conduction system. We'll talk about this again in a few minutes. All right, so, now let's start thinking a bit about the electrical activity of the entire heart. We've been discussing the electrical activity of the nodes in particular. Now we want to consider how we can find out what the electrical activity if the entire heart is. You can do this by placing electrodes on the surfaces of the body. These electrons will pick up the depolarization of the entire atria or the depolarization of the ventricles. Let's see what we mean by this. We said that we the electrical firing is unidirectional within this electrical conductive system. First the SA node fires. After the SA node fires, there is depolarization of the atria. The depolarization spreads across all of the atrial cells, the contractile cells of the atria. It does so by moving through the gap junctions located between the cells. When the depolarization reaches the AV node, there's a slight pause, and then the AV node fires. After the AV node fires, the electrical signal is sent across the AV boundary. That is across the cardiac skeleton into the septum. It follows the Bundle of His within the septum in both the left and the right branches and then down through the Purkinje fibres and up the walls of the ventricles. The depolarization of the heart wall occurs also in a very specific manner. There is depolarization from the inside of the wall to the outside. So we depolarize along what's called the endocardium, that's the inner portion of the wall, out to the outer portion of the wall, which is called the epicardium. So we have movement then of the electrical signal through the ventricles and out though the walls of the ventricles. As we said, repolarization will occur in the opposite direction. It moves from the outside of the walls towards the inside of the walls, from epicardium to endocardium, and from the apex which is the tip of the heart up towards the base which is here at the top of the ventricles. This electrical activity can be picked up by the electrodes placed on the surface of the body. We do not see the deflections that would be due just simply to the activity of the nodes. But we can see the summation of all the changes across the contractile cells, that is the cells of the atrium and the cells of the ventricle Because they're sufficiently large. When we sum all of that electrical activity together, then it is detected by a surface electrode. This trace that is recorded over time. This is called the electrocardiogram. Let's see what that looks like. The electrocardiogram is what's diagrammed here. The first thing that we notice is that there is a positive deflection. This is called the P wave. The P wave is the atrial depolarization. This is the sum of all of the contractile cells within the atria that are now depolarizing. There's then an isoelectric interval. Then we start the QRS complex. The QRS complex is ventricular depolarization. The AV node fires, and then the ventricles depolarize. Following the QRS complex, there is another isoelectric interval called the ST interval. We'll talk about the ST interval in a second. Then another wave, a positive wave, called the T wave, occurs. The T wave is ventricular repolarization. This is where all of the cells now are repolarizing within the ventricle. So a couple things to notice. So we said that there is a PR interval. That these intervals are timed, like the entire sequence is timed. If you look at this electrocardiogram on the x axis, this is the millivolts. This is the actual, potentials that you're recording. Along the x axis is time. This is a timed sequence of events. The PR segment is the time between when the SA node fires and the AV node fires. The ST segment is essentially phase 2 of the fast action potential. This is that isoelectric period where calcium is entering the cells and potassium is leaving the contractile cells. We have no change because of the positive charges entering and the positive charges leaving the cells. That's an isoelectric event. It's phase 2 of the fast action potential. The R-R period is heart rate. This is called an ECG or electrocardiogram. If we were to look at this tracing for someone who is running, what are the intervals that may change in time? Let's think about that. The first thing is is that we have to repolarize the heart faster so that we can have the next beat. So the very first thing that must change would be that that ST segment has to shorten. Phase 2 of the contractual myocyte's action potential phase 2 must shorten. So, the ST interval would be one of the segments would shorten. The second phase that might shorten would be, obviously, R-R. That has to shorten because we are increasing heart rate. So R-R will shorten. What's the third phase that's going to shorten? Let's think about that. The third phase that shortens is the movement of depolarization through the atria. It's how quickly the atria depolarizes. The atria will depolarize slightly faster. THat means that we will have a slightly shorter PR segment. The PR segment also shortens. What about the QRS? Turns out that the time it takes for the ventricles to depolarize will not change. Our change is so slight that we really can't pick it up on the ECG. We have three segments then which are changing: the R-R, which is heart rate, the ST which is the time between the depolarization and repolarization. We must shorten that in order to speed up the heart rate. And then we also can see some shortening of the PR segment. That is the time for the electrical activity to move through the atrium. Right,so let's have a little bit of terminology. The rhythm if it's initiated by the SA node, no matter what its rate, whether it's tachycardia, bradycardia or normal rate, this is called a sinus rhythm. For every P wave you will have a QRS complex following it, and then a T wave. Under certain conditions, you can have an ectopic foci or you can have some rogue cells which all of a sudden start firing. They're no longer listening to the beat of the fastest node. The fastest node is the SA node, and it usually sets the heart rate for the entire heart. Under these conditions the second set of cells, rogue cells are firing. This is called an ectopic foci. These foci can interfere with the sequential movement of electrical activity that we have just described. When that occurs, you can get arrythmias, you can get a skipped beat, you can have improper filling of the the chambers either of the atria, if it occurs in the atria, or of the ventricle, if it occurs in the ventricle. And under these conditions, if the chamber is contracting too rapidly because of an arrhythmia, then you may not be able to fill it. If this occurs in the ventricle, this could be lethal. You can have a heart attack. The other thing that we have to remember then are the electrical activities of the entire heart can be observed on the clinical ECG. That the time intervals, as well as whether a specific wave occurs gives information to the cardiologist as to how well the electrical conduction system of the heart is performing. There are some diseases where for instance, it takes too long for the ventricles to depolarize. So you will have a widening of the QRS. Or you can have other diseases where you have problems with repolarization of the heart. Under those conditions then it affects the T wave and the ST segment. All right, so let's look at a case. So our case is Mrs. R. She's 80 years old. Her normal resting heart rate is 85 beats per minute. She usually goes to the gym every day and she works out on an electrical stepper. On Friday, she was unable to do her morning exercises. She got up in the morning and didn't feel very well. By the time she got to the gym, she tried to get onto the electrical stepper, but she just couldn't get enough energy and was unable to do her exercises. She felt so badly that she decided to go and see her cardiologist. When she came in, he took her heart rate. Her heart rate was 30 beats per minute. She had bradycardia. Is this due to athletic training? No. Her normal resting heart rate was 85 on Thursday and on Friday it was 30. So, something dramatic had happened to the electrical conduction system within her heart. He decided to run electrocardiogram to see what changes had occurred within her heart. The electrocardiogram is shown here. On the Y-axis we have millivolts. On the X-axis we have time. As you can see, there are P waves present. The P waves have a very set time interval. So the P waves are occurring. That means the SA node is firing. The SA node is firing. It's firing on a regular basis. She has a normal SA node. But then if you look at the R in the QRS complex, there's a P wave followed by a QRS here, but then we have a P, which is not followed by the QRS complex. Then we have another P which again, is not followed by the QRS. Also note that the R to R intervals are longer than the P to P intervals. So, the R to R intervals are more regular but they occur in much longer intervals than the P-P intervals. This means that they have a different pacemaker. We've somehow uncoupled the electrical activity that's occurring the atria from the electrical activity that's occurring in the ventricle in this particular heart. That occurs if there is a complete block at the AV node. The AV node is not taking the information and listening to the pace which is set by the SA node. Instead, the atria are contracting at one pace, but the ventricles at a much slower pace. The new pacemaker, is a pacemaker that's gives her a 30 bpm. That new pacemaker would be the, HIS bundle or the Purkinjes fibers. Okay, so what are our key concepts? The first is, each heartbeat or one cardiac cycle involves electrical activation of the atria and the ventricles in the right and the left chambers. Secondly, that the action potential of the pacemaker and the contractile cells differ. They're both cardiac myocytes but their action are very different. In the pacemakers, the action potential is 150 milliseconds. There is an unstable resting membrane potential. In the cardiac myocyte that’s contractile, the time duration of the action potential is 200 to 220 milliseconds. There's a stable resting membrane potential. The pacemaker cells have an unstable resting membrane potential. The SA node is the fastest pacemaker in the heart. In the normal heart it sets the beat. All of the other pacemakers are entrained by the SA node. They follow the SA node beat. Fourth, our heart rate is determined by the autonomic nervous system. The sympathetic nervous system increases heart rate, speeds up heart rate. It acts through the beta-1 adrenergic receptors. The parasympathetic system slows heart rate. It is the brake for the system It's acting through vagus innervation or the vagal innervation. It activates the muscarinic receptors which are present on the heart. Five, the electrocardiogram is the sum of the electrical activity of the entire heart. The P waves depict the atrial depolarization, The QRS complex depicts the ventricular depolarization. The T wave is the ventricular repolarization. And six, disease of the electrical conduction system can be manifested by changes in the electrocardiogram itself. Both the timing, and whether or not a specific wave is occurring tells the cardiologist what possible disease process is/has occurred within the electrical conduction system. Okay, so the next time we come in, we're going to talk about how electrical conduction system coordinates the contractile activities of the heart. Okay, so see you then.
