Understanding the Cardiac Cycle and Physiology

We refer to one beat of the heart as the cardiac cycle, and we divide the cardiac cycle into two phases. Both of these phases are based on... actions that occur in the ventricles, not the atria, although of course the atria are also doing things at the same time. So we refer to these phases as systole, which is of course ventricular contraction and eventually ejection, and diastole, which refers to ventricular relaxation, and this is the time in which the ventricles fill with blood. The heart beats about 72 beats per minute, and that means that each beat lasts about 0.8 seconds. And of that 0.8 seconds, about 0.3 is spent in systole and 0.5 is spent in diastole. So each of these phases, systole and diastole, are further divided into two subdivisions. So if we look at systole, what we see is that the first division would be isobolumetric ventricular contraction. And we see that illustrated in this diagram from our text in the lower left-hand side of our slide. So if you follow the pointer, the cursor, what you see is that the ventricles are contracting, but for a very brief second, then the pressure is simply increasing inside the ventricles, but the blood's not going anywhere. And so as the pressure increases, we notice that all four of the valves are closed. The right atrioventricular valve, the left atrioventricular valve, the pulmonary semilunar valve, and the atrial semilunar valve are all closed. all four closed. Then, and to illustrate this, we need to move to our right just slightly, we see that the pressure in the ventricles is going to exceed the pressure in both the pulmonary trunk and the aorta. And as the pressure in the ventricles exceeds the pressure in those vessels, then the semilunar valves open, both the pulmonary semilunar valve here and the aortic semilunar valve here, and the blood moves. from the ventricles into these vessels going all the way through the body, in the case of the aorta, or to the lungs in the case of the pulmonary trunk. And we refer to this, of course, as ventricular ejection. And the volume of blood that leaves during this period of time is known as the stroke volume. And of course, the stroke volume, or we probably realize that the stroke volume, doesn't represent... all the blood that was found in the ventricle. There is some blood that does remain there following a contraction. So just to review, if we look at the atrioventricular valves and the semilunar valves, called the aortic and pulmonary valves here, during isovolumetric ventricular contraction, they're both closed. During ventricular ejection, the atrioventricular valves are still closed, but the semilunar valves open. The second part of the cardiac cycle is, of course, diastole, which represents ventricular relaxation. And like systole, it can be divided into two different sections. And so if we start here at the left... left hand side in our diagrams, what we see is that when the ventricles first relax, and again, this is not showing what's happening in the atria, but rather systole and diastole refer to relaxation and contraction of the ventricles. So at first, all the valves are closed. The atrioventricular valves and the aortic and pulmonary semilunar valves are all closed because the ventricles have relaxed, but the pressure in the ventricles has not yet dropped below the pressure in the atria. So what does occur, what has occurred here from the last stage is that the semilunar valves have closed. These arrows here indicate that the pressure... in the pulmonary trunk and the aorta is greater than in the ventricles, so the blood's trying to go backwards, but it's prevented from doing so by the aortic and pulmonary valves. The second step of diastole is referred to as ventricular filling. Ventricular filling occurs when the pressure in the atria exceed the pressure in the ventricles. At this particular point, the atrioventricular valves on both the the right and left sides open, blood moves from the atria down to the ventricles. And interestingly, about 80% of the blood that's going to fill the ventricles moves during this time. The last 20% of the blood, 10 to 20% perhaps, is transferred from the atria down into the ventricles when the atria contract, giving this so-called atrial kick. This last little bit of blood is transferred into the ventricles during the last stage of ventricular filling. Figure 1219, which is of course depicted on this slide, has a number of details related to the cardiac cycle. If we look at our graph, what we notice is that on the top half of the graph, we're tracking pressure. On the bottom half of the graph, we're tracking the left ventricular volume. The same events would occur in the right ventricle, but the overall pressures would be lower. So let's start out with the top half of our graph, and let's first follow the... atrial pressure which is shown in the blue line here and what we see is that atrial okay so we're starting out in diastole and then the end of diastole and then we go through systole and then we go through another complete diastole making our way all the way back around to where we were at the beginning of our cardiac cycle here so if we're tracking left atrial pressure we see that it goes up and up and up gradually and then Then seven here represents atrial contraction. And so atrial contraction is pushing the last 10 to 20% of blood down into the ventricle. And so left atrial and left ventricular pressure track together here perfectly, increasing slightly as the atria contract. Then the ventricle contracts. And when the ventricle contracts, then the pressures diverge instantly. And so we have this tremendous increase in the... the ventricular pressure, whereas the atrial pressure decreases as the atria relaxes. And so the atria, of course, is filling during this time. And the ventricular pressure goes up and up and up and up. The pressure was already pretty high in the aorta. But what we notice is at this particular point, the ventricular pressure exceeds the aortic pressure. And so, of course, at that point, the similar... semilunar valves, the aortic semilunar valve, and the same thing would be occurring in a pulmonary semilunar valve on the right side of the heart, is opening. And then, of course, once it's open, then the pressure in the left ventricle and the aorta are identical. And so we go up and up and up and over the top here. And then the ventricle starts to relax. We're still in systole, but it begins to relax. And so we have a decrease, a decrease, a decrease, a decrease. And at this point, then the pressure in the ventricle declines below. the pressure that we see in the aorta. And the ventricular pressure continues to decline, down, down, down, down, down, down. Now, interestingly, what we see here is this little notch, this dichroic notch. And the notch is the result of the closure of the aortic semilunar valve. So the pressure is transferred from the ventricle into the aorta. The aorta stretches ever so slightly. And then those semilunar valves or the aortic semilunar valve snap. snap shut behind that blood and following that the aorta contracts ever so slightly. And when I say contract, I don't mean the smooth muscle contracts. What I mean is the elastic tissue within the aorta springs back to its original shape. That pressure is transferred into the blood in the aorta. So you get this little peak called the dichroic notch. as that aortic elastic tissue springs back to its original shape. And then the aortic pressure goes down and down and down and down until you have the second ventricular contraction. We note, of course, that the aortic pressure is always pretty high, but it cycles through the cardiac cycle from a low, just before ventricular contraction, to a high following the closure of those semilunar valves. And then we go all the way back down. following ventricular pressure, if you're following along with the cursor there, at this point, the ventricular pressure drops below aortic pressure, and so we're in diastole at this point, and of course, at this point, the aortic semilunar valve would open, and blood would move from the aorta into the ventricle, excuse me, from the atria into the ventricle, and so the pressures in the ventricle and the atria would be exactly the same, and then we find ourselves over here. to where we started our discussion a moment ago. If we drop back down here, then what we, to the lower half of our diagram, we're tracking the volume. And so there's no real surprises in the volume. This is the ventricular volume. What we see is that it's filling, filling, filling, and then eight represents that atrial kick, so to speak, that last 10 to 20 minutes. 20% that's contributed by atrial contraction. This is our end diastolic volume. This is the amount of blood that's going to be in the ventricle before contraction. Contraction occurs, and the volume in the ventricle goes down, down, down, down, down, down, down to here. This is as low as it's going to get. So this is the end-systolic volume. And as I mentioned previously, there is a volume of blood left in the ventricle following contraction. And then the ventricle starts to fill again, and it goes up and up and up. up and up and up and then of course we get you know we're back to where we started we get that contribution from the atrial contraction right there so below here there's not much else to note other than we can line up our p wave we already knew our p wave represented atrial depolarization and therefore contraction and so that matches up nicely we knew our qrs complex represented ventricular depolarization followed by contraction so that matches up nicely with what we see above and then we knew the the T wave represented ventricular repolarization, which of course is representative of ventricular relaxation, so that matches up nicely with what we see above. The heart sounds are shown in this yellow line here, lub-dub, we'll talk about those in a minute, that relate to the opening and closing of the valves, but those match up nicely with the valve opening and closings that we just mentioned. I encourage you to go through this figure, I know it's time consuming, but but there's perhaps no other tool that's more effective in helping us to learn the events in the cardiac cycle other than that figure 1219 on page 379. What we just described in figure 1219 were the pressures and volumes found in the left ventricle. What we notice is that if we look at the right ventricle, we see a nearly identical pattern, so we don't go back and talk about all those steps again, but we do notice that the pressure is still there. pressures are dramatically lower. And so on the right side, systolic and diastolic pressures are typically average at 25 millimeters of mercury and 10 millimeters of mercury, respectively. Whereas on the left-hand side, the systolic and diastolic pressures average 120 millimeters of mercury and 80 millimeters of mercury, respectively. So there's a dramatic difference in the pressures. And this is, of course, because on the right side of the heart... the blood is only going to the lungs through pulmonary circulation versus the left side of the heart where the blood's going through the entire body. We also notice that the right ventricular wall is, of course, much thinner than the wall on the left ventricle, as you certainly have long been aware of. We see the pressures listed there during the various steps in the figure on the bottom portion of this slide. Those are identical. We see the pulmonary artery pressure in green and the right ventricular pressure in orange. Those follow an identical pattern to what we just talked about in more detail. However, the absolute volume or absolute number is much lower. What we notice is that the heart makes certain sounds that can be heard with a stethoscope. And so that lub-dub, lub-dub, lub-dub sounds that we hear are the result of the closing of the valves. The lub sound is the closing of the atria ventricular valve. and the dub sound is the closing of the semilunar valves. These can sometimes be diagnostic for physiological problems, problems referred to as heart murmurs. Heart murmurs are the result of some problem associated with the heart. with the valve. The term heart murmur refers to some unusual sound that is distinguishable with a stethoscope, but the cause of those sounds are some sort of problem with the valves. And so as we look at the figure on the lower right-hand portion of our screen, we see that we have a normal open valve in the first part of A and then a closed valve in the second part of A. If we look over... at the right side of our diagram, part B, we see that in a stenotic valve, we have a narrowed valve. For some reason, the flaps of the valve are not as flexible as they should be. They don't open fully. And so this leads to turbulent as opposed to laminar flow. Laminar flow is a straight, non-curved flow, whereas turbulent flow is, of course, this flow in which the blood curls and makes these unusual patterns. And so that's one possibility for a heart murmur. Another possibility, and maybe one that's more common, would be a leaky valve. And so in this particular case, we should see what we see here in the bottom of A. So the blood is completely... prevented from going back through, for instance, the atrioventricular valves. But in the case of the atrioventricular valves, in a leaky valve situation, they don't close completely as they should. And so some blood makes its way back through, and you have this turbulent backflow that also results in a different type of heart murmur. The volume of blood pumped by the heart, which is usually expressed in liters per minute, is referred to as the cardiac output. So cardiac output then must be equal to the heart rate times the stroke volume, the volume of blood that's pumped with every contraction of the ventricle. What we see is that typical resting cardiac output looks something like what we have on the screen. So we have 72 beats per minute, and then we have about 0.07 liters per minute. per beat, so 0.07 times 72, equals 5 liters of blood that's pumped per minute. So the average volume of blood in a human being is about 5.5 liters, which means that the total blood volume is being pumped through the body about once every 60 seconds. Now this, of course, changes in response to exercise. And so what we see is that highly trained athletes can achieve volumes of of somewhere in the neighborhood of 35 liters per minute, whereas even a sedentary individual following exercise, the cardiac output increases to somewhere in the neighborhood of 20 to 25 liters per minute. We now start to think about what controls the cardiac output, and there are two factors that control cardiac output. One is heart rate, and the other, of course, would have to be stroke volume. Both of these are regulated by the body. and we'll talk about the mechanisms of regulation now. In the case of heart rate, which is the first one that we'll talk about, the heart will beat at about 100 beats per minute in the absence of any input to the SA node. What we see is that the resting heart rate is more influenced by parasympathetic than sympathetic stimulation, and so that reduces the heart rate, the average heart rate, to about 70 beats per minute. That... rate can be either increased by sympathetic stimulation or decreased by parasympathetic stimulation, as we see depicted in this diagram in the lower left-hand side of our screen. What we see is that plasma epinephrine, which is, of course, acting in coordination with the sympathetic stimulation, also increases heart rate. Epinephrine is binding to the same receptors as norepinephrine released by the sympathetic. nervous system. The increase in heart rate is accomplished in an interesting way. If we look over at this diagram in the lower right-hand side of our slide, this of course is the membrane potential in a single cell of the SA node during a beat of the heart. And so A is that familiar pattern that we saw back in a previous section of this chapter, and we talked about the role of all the different channels. Well, now we get to notice this. So B is of course the SA node. SA node under sympathetic stimulation. And so what you see is that the overall size of this curve is narrowed, and it takes less time. And so this means that more action potentials are being generated per unit time. Everything is more compact. And the reason for that is that those F-type channels, the so-called funny channels that are open at negative instead of positive charges, and those are sodium channels, as you recall, are... open, they're open more as a result of sympathetic stimulation. And so that means that the cell achieves depolarization more rapidly than it would in the control situation, which is shown in A. The opposite occurs in the case of parasympathetic stimulation. In the case of parasympathetic stimulation, the cell permeability to potassium is increased. This means that more positive charges, of course, are leaving the cell. The overall charge of the cell is hyperpolarized relative to the control situation. And so this means it takes the cell longer to achieve threshold and undergo an action potential. And so under sympathetic stimulation, the action potentials that are generated increase in number. Under parasympathetic stimulation, they decrease in number. We now turn our attention towards the second factor that influences cardiac output, stroke volume. What we notice is that stroke volume is influenced by three separate factors. One, the change in the end diastolic volume, which is also known as the preload. In other words, it's the amount of blood that's present in the ventricles before the ventricle starts to contract. Number two, we of course notice that input from the sympathetic nervous system influences stroke volume. And number three, interest... something referred to as afterload influences stroke volume. That is the pressure in the arteries against which the ventricles are pumping. So we begin with the first of those mechanisms here on this particular slide, the end diastolic volume. volume. Interestingly, the mechanism that controls the mechanism by which endolus diastolic volume influences stroke volume is referred to as the Frank-Starlink mechanism of the heart because of its discovery by Dr. Frank and Dr. Starling. Dr. Otto Frank, a German physiologist, is shown in the upper right-hand portion of this particular slide. And the bottom line is the Frank-Starlink mechanism. of the heart is explained in this little graph that we see at the bottom of our slide. Now, here we see a normal resting value in diastolic volume, which is about 140 milliliters of blood. And if there's 140 milliliters of blood in the ventricle when it begins to contract, then the output is about 75 milliliters of blood. As you already know. the stroke volume is less than the end diastolic volume. Some blood remains in the ventricle after each contraction. However, if we add additional blood to the heart during the filling period, then here we end up with 210 or so milliliters of blood. Then we increase the amount of blood that's ejected. We increase it perhaps to 215 mils here. So this means if you put more blood in the ventricle, then it ejects more blood. each beat. This is extremely important in the function of the heart because imagine this, we have two completely separate circuits. Imagine that one of those circuits, say the right hand side of the heart, suddenly started to pump more blood. So that blood would be sent to the left side. If the left side doesn't start pumping blood more rapidly, then that blood accumulates in the left hand side of the heart, backed up waiting to go through the heart. This of course would cause tremendous problems. physiology and physiologically and so it's absolutely necessary that both sides remain completely coordinated and they do remain completely coordinated as a result of this frank starling mechanism of the heart now how do you explain this mechanistically well it's a it's a matter of a length tension relationship so we noticed in the case of skeletal muscle that the length tension relationship was such that the normal resting length of a muscle is the the L of zero, the length at which you're going to get the absolute maximal force from that muscle. That's not so in the case of the heart. What we see is that at a normal resting value, the length tension relationship between the myosin and actin in heart cells is shifted over to the beginning of that curve. So if you add more blood, then you stretch the chamber, the ventricle, and you pull apart the thin filaments along the thick filament. And when you do that, you take it closer to that optimal length at which it's going to contract more powerfully. And so that explains this Frank Starling mechanism. Now, it is worth noting, as we point out on our slide, that this relationship is a little more complex in cardiac muscle than it was back in skeletal muscle. For instance, what we see is that in skeletal muscle... it was just a matter of the degree of overlap between thick and thin filaments. In the case of cardiac muscle, there's multiple factors at play. One is as we stretch out those sarcomeres, then we're decreasing the space between the thick and thin filaments. We're increasing the sensitivity of troponin to calcium. We're even increasing the release of calcium from the sarcoplasmic reticulum. So it's a bit more complicated in cardiac muscle versus skeletal muscle. There are multiple factors that are influencing. this length tension relationship. We now turn our attention to the last factor that influences stroke volume, which is sympathetic regulation. Sympathetic regulation leads to increased contractility. And what this means is that with each beat of the heart, the blood both goes in faster and comes out faster, and there's a higher volume of blood that's going in and coming out. It's best explained probably by looking at this diagram in the lower right-hand side of our slide. The green line... represents the control. force that's developed during contraction in the contraction of a ventricle. The orange line represents the force that's generated under sympathetic stimulation and so the force both starts sooner increases more rapidly and achieves an overall greater magnitude. than under a control situation. And so this is the influence of sympathetic regulation. It's important to keep in mind that this is independent. This is in addition to the Frank Starling mechanism of the heart that we just finished talking about. relationship is always impacting the stroke volume but this is in addition to that in addition to the Frank Starling mechanism of the heart so this is this is best that the sympathetic effects on stroke volume are probably best observed by looking at something referred to as the ejection fraction The ejection fraction is the stroke volume divided by the end diastolic volume. And so under resting conditions, the ejection fraction is 50% to 75% of the blood. It's just 50% to 75%, of course. 50% to 75% of the blood that's present in the end diastolic volume is ejected, but this increases significantly in response to sympathetic stimulation. And then, of course, as we mentioned, it also speeds up ventricular contraction as we go. can see in 1225B there. If we think about the influence of sympathetic regulation on stroke volume, then we can see a nice illustration of that in the lower left-hand figure at the bottom of our page. So the green line represents the normal resting value. And so we're, of course, seeing the Frank Starling mechanism of the heart here. As we increase the overall end diastolic volume, we're increasing the stroke volume. But then... As we look at the orange line, what we see is that we're observing the increased contractility under sympathetic regulation. So at every end diastolic volume, we are ejecting more. Our ejection fraction is greater. We're ejecting more blood than we would be under the control scenario, which, of course, does not have the influence of sympathetic regulation. The mechanism by which sympathetic regulation impacts overall contractility can be explained. by looking at the effect of some protein kinases on these various impacts of cardiac cell physiology. We see it depicted nicely in this diagram. So epinephrine and norepinephrine are binding to beta adrenergic receptors, and via a G-protein coupled mechanism are activating adenylal cyclase, which in turn elevates cyclic AMP levels in the cell, which activates protein kinases. Once the protein kinases are active, then they have five impacts on these various intracellular aspects of cardiac cell physiology. They increase the speed at which the L-type calcium channels open. We're certainly familiar with those at this point. They increase the speed at which the ryanodine receptor channels in the sarcoplasmic reticulum are opening and releasing calcium. They increase the thin filament activation by... calcium of troponin, they enhance cross-bridge cycling and thick and thin filament sliding and therefore force generation. And then lastly, but very importantly, they increase the speed at which the calcium is transported back into the sarcoplasmic reticulum. All these factors then contribute to both the increased stroke volume and the increased speed at which the generation of force and therefore the ejection of blood in the stroke volume takes place. place. Lastly, the third factor that we just mentioned that controls the amount of blood that's ejected with each stroke volume is the so-called afterload. In other words, that would be the pressure that's... found in the arteries that the left and right ventricles are pumping blood into. So generally, this has a minimal influence on cardiac output because it's typically It's typically constant. It typically changes very little as a result of some physiological factors, the ability of the smooth muscle found in the blood vessels to constrict and dilate. But we do see in some cases where a person is suffering from chronically high blood pressure, this does have an overall negative impact on the cardiac output. It can be very damaging physiologically. But for the most part, it has... very minimal impacts on the cardiac output in a healthy individual. So we close this discussion by summarizing the impacts that we just went over related to cardiac output. So if we increase the end diastolic volume via the Frank Starling mechanism of the heart, we increase the stroke volume and increase the cardiac output. If we increase the sympathetic activity and therefore increase the sympathetic activity in the nervous system, we increase the sympathetic activity in nerves going to the heart, we both increase the stroke volume and we increase the heart rate. If we increase plasma epinephrine, then we increase the stroke volume and increase the heart rate via the identical mechanisms that we just talked about to what we see if we actually increase the activity of the sympathetic nerves. And of course, if we decrease the parasympathetic activity of the nerves that are headed to the heart, mostly the atria, then we increase the heart rate. rate, we see that we don't have any impact on the overall stroke volume because those parasympathetic nerves, as you remember, are going to the atria, impacting the sinoatrial node, but they're not impacting the ventricles.

And of that 0.8 seconds, about 0.3 is spent in systole and 0.5 is spent in diastole. So each of these phases, systole and diastole, are further divided into two subdivisions. So if we look at systole, what we see is that the first division would be isobolumetric ventricular contraction. And we see that illustrated in this diagram from our text in the lower left-hand side of our slide. So if you follow the pointer, the cursor, what you see is that the ventricles are contracting, but for a very brief second, then the pressure is simply increasing inside the ventricles, but the blood's not going anywhere.

And so as the pressure increases, we notice that all four of the valves are closed. The right atrioventricular valve, the left atrioventricular valve, the pulmonary semilunar valve, and the atrial semilunar valve are all closed. all four closed. Then, and to illustrate this, we need to move to our right just slightly, we see that the pressure in the ventricles is going to exceed the pressure in both the pulmonary trunk and the aorta.

And as the pressure in the ventricles exceeds the pressure in those vessels, then the semilunar valves open, both the pulmonary semilunar valve here and the aortic semilunar valve here, and the blood moves. from the ventricles into these vessels going all the way through the body, in the case of the aorta, or to the lungs in the case of the pulmonary trunk. And we refer to this, of course, as ventricular ejection.

And the volume of blood that leaves during this period of time is known as the stroke volume. And of course, the stroke volume, or we probably realize that the stroke volume, doesn't represent... all the blood that was found in the ventricle.

There is some blood that does remain there following a contraction. So just to review, if we look at the atrioventricular valves and the semilunar valves, called the aortic and pulmonary valves here, during isovolumetric ventricular contraction, they're both closed. During ventricular ejection, the atrioventricular valves are still closed, but the semilunar valves open. The second part of the cardiac cycle is, of course, diastole, which represents ventricular relaxation.

And like systole, it can be divided into two different sections. And so if we start here at the left... left hand side in our diagrams, what we see is that when the ventricles first relax, and again, this is not showing what's happening in the atria, but rather systole and diastole refer to relaxation and contraction of the ventricles. So at first, all the valves are closed.

The atrioventricular valves and the aortic and pulmonary semilunar valves are all closed because the ventricles have relaxed, but the pressure in the ventricles has not yet dropped below the pressure in the atria. So what does occur, what has occurred here from the last stage is that the semilunar valves have closed. These arrows here indicate that the pressure...

in the pulmonary trunk and the aorta is greater than in the ventricles, so the blood's trying to go backwards, but it's prevented from doing so by the aortic and pulmonary valves. The second step of diastole is referred to as ventricular filling. Ventricular filling occurs when the pressure in the atria exceed the pressure in the ventricles. At this particular point, the atrioventricular valves on both the the right and left sides open, blood moves from the atria down to the ventricles.

And interestingly, about 80% of the blood that's going to fill the ventricles moves during this time. The last 20% of the blood, 10 to 20% perhaps, is transferred from the atria down into the ventricles when the atria contract, giving this so-called atrial kick. This last little bit of blood is transferred into the ventricles during the last stage of ventricular filling.

Figure 1219, which is of course depicted on this slide, has a number of details related to the cardiac cycle. If we look at our graph, what we notice is that on the top half of the graph, we're tracking pressure. On the bottom half of the graph, we're tracking the left ventricular volume.

The same events would occur in the right ventricle, but the overall pressures would be lower. So let's start out with the top half of our graph, and let's first follow the... atrial pressure which is shown in the blue line here and what we see is that atrial okay so we're starting out in diastole and then the end of diastole and then we go through systole and then we go through another complete diastole making our way all the way back around to where we were at the beginning of our cardiac cycle here so if we're tracking left atrial pressure we see that it goes up and up and up gradually and then Then seven here represents atrial contraction.

And so atrial contraction is pushing the last 10 to 20% of blood down into the ventricle. And so left atrial and left ventricular pressure track together here perfectly, increasing slightly as the atria contract. Then the ventricle contracts.

And when the ventricle contracts, then the pressures diverge instantly. And so we have this tremendous increase in the... the ventricular pressure, whereas the atrial pressure decreases as the atria relaxes.

And so the atria, of course, is filling during this time. And the ventricular pressure goes up and up and up and up. The pressure was already pretty high in the aorta. But what we notice is at this particular point, the ventricular pressure exceeds the aortic pressure. And so, of course, at that point, the similar...

semilunar valves, the aortic semilunar valve, and the same thing would be occurring in a pulmonary semilunar valve on the right side of the heart, is opening. And then, of course, once it's open, then the pressure in the left ventricle and the aorta are identical. And so we go up and up and up and over the top here. And then the ventricle starts to relax.

We're still in systole, but it begins to relax. And so we have a decrease, a decrease, a decrease, a decrease. And at this point, then the pressure in the ventricle declines below. the pressure that we see in the aorta. And the ventricular pressure continues to decline, down, down, down, down, down, down.

Now, interestingly, what we see here is this little notch, this dichroic notch. And the notch is the result of the closure of the aortic semilunar valve. So the pressure is transferred from the ventricle into the aorta. The aorta stretches ever so slightly. And then those semilunar valves or the aortic semilunar valve snap.

snap shut behind that blood and following that the aorta contracts ever so slightly. And when I say contract, I don't mean the smooth muscle contracts. What I mean is the elastic tissue within the aorta springs back to its original shape.

That pressure is transferred into the blood in the aorta. So you get this little peak called the dichroic notch. as that aortic elastic tissue springs back to its original shape.

And then the aortic pressure goes down and down and down and down until you have the second ventricular contraction. We note, of course, that the aortic pressure is always pretty high, but it cycles through the cardiac cycle from a low, just before ventricular contraction, to a high following the closure of those semilunar valves. And then we go all the way back down.

following ventricular pressure, if you're following along with the cursor there, at this point, the ventricular pressure drops below aortic pressure, and so we're in diastole at this point, and of course, at this point, the aortic semilunar valve would open, and blood would move from the aorta into the ventricle, excuse me, from the atria into the ventricle, and so the pressures in the ventricle and the atria would be exactly the same, and then we find ourselves over here. to where we started our discussion a moment ago. If we drop back down here, then what we, to the lower half of our diagram, we're tracking the volume.

And so there's no real surprises in the volume. This is the ventricular volume. What we see is that it's filling, filling, filling, and then eight represents that atrial kick, so to speak, that last 10 to 20 minutes.

20% that's contributed by atrial contraction. This is our end diastolic volume. This is the amount of blood that's going to be in the ventricle before contraction.

Contraction occurs, and the volume in the ventricle goes down, down, down, down, down, down, down to here. This is as low as it's going to get. So this is the end-systolic volume. And as I mentioned previously, there is a volume of blood left in the ventricle following contraction. And then the ventricle starts to fill again, and it goes up and up and up.

up and up and up and then of course we get you know we're back to where we started we get that contribution from the atrial contraction right there so below here there's not much else to note other than we can line up our p wave we already knew our p wave represented atrial depolarization and therefore contraction and so that matches up nicely we knew our qrs complex represented ventricular depolarization followed by contraction so that matches up nicely with what we see above and then we knew the the T wave represented ventricular repolarization, which of course is representative of ventricular relaxation, so that matches up nicely with what we see above. The heart sounds are shown in this yellow line here, lub-dub, we'll talk about those in a minute, that relate to the opening and closing of the valves, but those match up nicely with the valve opening and closings that we just mentioned. I encourage you to go through this figure, I know it's time consuming, but but there's perhaps no other tool that's more effective in helping us to learn the events in the cardiac cycle other than that figure 1219 on page 379. What we just described in figure 1219 were the pressures and volumes found in the left ventricle.

What we notice is that if we look at the right ventricle, we see a nearly identical pattern, so we don't go back and talk about all those steps again, but we do notice that the pressure is still there. pressures are dramatically lower. And so on the right side, systolic and diastolic pressures are typically average at 25 millimeters of mercury and 10 millimeters of mercury, respectively.

Whereas on the left-hand side, the systolic and diastolic pressures average 120 millimeters of mercury and 80 millimeters of mercury, respectively. So there's a dramatic difference in the pressures. And this is, of course, because on the right side of the heart... the blood is only going to the lungs through pulmonary circulation versus the left side of the heart where the blood's going through the entire body. We also notice that the right ventricular wall is, of course, much thinner than the wall on the left ventricle, as you certainly have long been aware of.

We see the pressures listed there during the various steps in the figure on the bottom portion of this slide. Those are identical. We see the pulmonary artery pressure in green and the right ventricular pressure in orange.

Those follow an identical pattern to what we just talked about in more detail. However, the absolute volume or absolute number is much lower. What we notice is that the heart makes certain sounds that can be heard with a stethoscope.

And so that lub-dub, lub-dub, lub-dub sounds that we hear are the result of the closing of the valves. The lub sound is the closing of the atria ventricular valve. and the dub sound is the closing of the semilunar valves. These can sometimes be diagnostic for physiological problems, problems referred to as heart murmurs.

Heart murmurs are the result of some problem associated with the heart. with the valve. The term heart murmur refers to some unusual sound that is distinguishable with a stethoscope, but the cause of those sounds are some sort of problem with the valves.

And so as we look at the figure on the lower right-hand portion of our screen, we see that we have a normal open valve in the first part of A and then a closed valve in the second part of A. If we look over... at the right side of our diagram, part B, we see that in a stenotic valve, we have a narrowed valve. For some reason, the flaps of the valve are not as flexible as they should be. They don't open fully.

And so this leads to turbulent as opposed to laminar flow. Laminar flow is a straight, non-curved flow, whereas turbulent flow is, of course, this flow in which the blood curls and makes these unusual patterns. And so that's one possibility for a heart murmur.

Another possibility, and maybe one that's more common, would be a leaky valve. And so in this particular case, we should see what we see here in the bottom of A. So the blood is completely...

prevented from going back through, for instance, the atrioventricular valves. But in the case of the atrioventricular valves, in a leaky valve situation, they don't close completely as they should. And so some blood makes its way back through, and you have this turbulent backflow that also results in a different type of heart murmur. The volume of blood pumped by the heart, which is usually expressed in liters per minute, is referred to as the cardiac output. So cardiac output then must be equal to the heart rate times the stroke volume, the volume of blood that's pumped with every contraction of the ventricle.

What we see is that typical resting cardiac output looks something like what we have on the screen. So we have 72 beats per minute, and then we have about 0.07 liters per minute. per beat, so 0.07 times 72, equals 5 liters of blood that's pumped per minute.

So the average volume of blood in a human being is about 5.5 liters, which means that the total blood volume is being pumped through the body about once every 60 seconds. Now this, of course, changes in response to exercise. And so what we see is that highly trained athletes can achieve volumes of of somewhere in the neighborhood of 35 liters per minute, whereas even a sedentary individual following exercise, the cardiac output increases to somewhere in the neighborhood of 20 to 25 liters per minute.

We now start to think about what controls the cardiac output, and there are two factors that control cardiac output. One is heart rate, and the other, of course, would have to be stroke volume. Both of these are regulated by the body. and we'll talk about the mechanisms of regulation now. In the case of heart rate, which is the first one that we'll talk about, the heart will beat at about 100 beats per minute in the absence of any input to the SA node.

What we see is that the resting heart rate is more influenced by parasympathetic than sympathetic stimulation, and so that reduces the heart rate, the average heart rate, to about 70 beats per minute. That... rate can be either increased by sympathetic stimulation or decreased by parasympathetic stimulation, as we see depicted in this diagram in the lower left-hand side of our screen. What we see is that plasma epinephrine, which is, of course, acting in coordination with the sympathetic stimulation, also increases heart rate. Epinephrine is binding to the same receptors as norepinephrine released by the sympathetic.

nervous system. The increase in heart rate is accomplished in an interesting way. If we look over at this diagram in the lower right-hand side of our slide, this of course is the membrane potential in a single cell of the SA node during a beat of the heart. And so A is that familiar pattern that we saw back in a previous section of this chapter, and we talked about the role of all the different channels. Well, now we get to notice this.

So B is of course the SA node. SA node under sympathetic stimulation. And so what you see is that the overall size of this curve is narrowed, and it takes less time.

And so this means that more action potentials are being generated per unit time. Everything is more compact. And the reason for that is that those F-type channels, the so-called funny channels that are open at negative instead of positive charges, and those are sodium channels, as you recall, are...

open, they're open more as a result of sympathetic stimulation. And so that means that the cell achieves depolarization more rapidly than it would in the control situation, which is shown in A. The opposite occurs in the case of parasympathetic stimulation.

In the case of parasympathetic stimulation, the cell permeability to potassium is increased. This means that more positive charges, of course, are leaving the cell. The overall charge of the cell is hyperpolarized relative to the control situation. And so this means it takes the cell longer to achieve threshold and undergo an action potential. And so under sympathetic stimulation, the action potentials that are generated increase in number.

Under parasympathetic stimulation, they decrease in number. We now turn our attention towards the second factor that influences cardiac output, stroke volume. What we notice is that stroke volume is influenced by three separate factors. One, the change in the end diastolic volume, which is also known as the preload. In other words, it's the amount of blood that's present in the ventricles before the ventricle starts to contract.

Number two, we of course notice that input from the sympathetic nervous system influences stroke volume. And number three, interest... something referred to as afterload influences stroke volume.

That is the pressure in the arteries against which the ventricles are pumping. So we begin with the first of those mechanisms here on this particular slide, the end diastolic volume. volume. Interestingly, the mechanism that controls the mechanism by which endolus diastolic volume influences stroke volume is referred to as the Frank-Starlink mechanism of the heart because of its discovery by Dr. Frank and Dr. Starling. Dr. Otto Frank, a German physiologist, is shown in the upper right-hand portion of this particular slide.

And the bottom line is the Frank-Starlink mechanism. of the heart is explained in this little graph that we see at the bottom of our slide. Now, here we see a normal resting value in diastolic volume, which is about 140 milliliters of blood.

And if there's 140 milliliters of blood in the ventricle when it begins to contract, then the output is about 75 milliliters of blood. As you already know. the stroke volume is less than the end diastolic volume.

Some blood remains in the ventricle after each contraction. However, if we add additional blood to the heart during the filling period, then here we end up with 210 or so milliliters of blood. Then we increase the amount of blood that's ejected.

We increase it perhaps to 215 mils here. So this means if you put more blood in the ventricle, then it ejects more blood. each beat.

This is extremely important in the function of the heart because imagine this, we have two completely separate circuits. Imagine that one of those circuits, say the right hand side of the heart, suddenly started to pump more blood. So that blood would be sent to the left side.

If the left side doesn't start pumping blood more rapidly, then that blood accumulates in the left hand side of the heart, backed up waiting to go through the heart. This of course would cause tremendous problems. physiology and physiologically and so it's absolutely necessary that both sides remain completely coordinated and they do remain completely coordinated as a result of this frank starling mechanism of the heart now how do you explain this mechanistically well it's a it's a matter of a length tension relationship so we noticed in the case of skeletal muscle that the length tension relationship was such that the normal resting length of a muscle is the the L of zero, the length at which you're going to get the absolute maximal force from that muscle. That's not so in the case of the heart. What we see is that at a normal resting value, the length tension relationship between the myosin and actin in heart cells is shifted over to the beginning of that curve.

So if you add more blood, then you stretch the chamber, the ventricle, and you pull apart the thin filaments along the thick filament. And when you do that, you take it closer to that optimal length at which it's going to contract more powerfully. And so that explains this Frank Starling mechanism.

Now, it is worth noting, as we point out on our slide, that this relationship is a little more complex in cardiac muscle than it was back in skeletal muscle. For instance, what we see is that in skeletal muscle... it was just a matter of the degree of overlap between thick and thin filaments.

In the case of cardiac muscle, there's multiple factors at play. One is as we stretch out those sarcomeres, then we're decreasing the space between the thick and thin filaments. We're increasing the sensitivity of troponin to calcium. We're even increasing the release of calcium from the sarcoplasmic reticulum.

So it's a bit more complicated in cardiac muscle versus skeletal muscle. There are multiple factors that are influencing. this length tension relationship. We now turn our attention to the last factor that influences stroke volume, which is sympathetic regulation.

Sympathetic regulation leads to increased contractility. And what this means is that with each beat of the heart, the blood both goes in faster and comes out faster, and there's a higher volume of blood that's going in and coming out. It's best explained probably by looking at this diagram in the lower right-hand side of our slide. The green line...

represents the control. force that's developed during contraction in the contraction of a ventricle. The orange line represents the force that's generated under sympathetic stimulation and so the force both starts sooner increases more rapidly and achieves an overall greater magnitude. than under a control situation.

And so this is the influence of sympathetic regulation. It's important to keep in mind that this is independent. This is in addition to the Frank Starling mechanism of the heart that we just finished talking about. relationship is always impacting the stroke volume but this is in addition to that in addition to the Frank Starling mechanism of the heart so this is this is best that the sympathetic effects on stroke volume are probably best observed by looking at something referred to as the ejection fraction The ejection fraction is the stroke volume divided by the end diastolic volume. And so under resting conditions, the ejection fraction is 50% to 75% of the blood.

It's just 50% to 75%, of course. 50% to 75% of the blood that's present in the end diastolic volume is ejected, but this increases significantly in response to sympathetic stimulation. And then, of course, as we mentioned, it also speeds up ventricular contraction as we go. can see in 1225B there. If we think about the influence of sympathetic regulation on stroke volume, then we can see a nice illustration of that in the lower left-hand figure at the bottom of our page.

So the green line represents the normal resting value. And so we're, of course, seeing the Frank Starling mechanism of the heart here. As we increase the overall end diastolic volume, we're increasing the stroke volume.

But then... As we look at the orange line, what we see is that we're observing the increased contractility under sympathetic regulation. So at every end diastolic volume, we are ejecting more. Our ejection fraction is greater. We're ejecting more blood than we would be under the control scenario, which, of course, does not have the influence of sympathetic regulation.

The mechanism by which sympathetic regulation impacts overall contractility can be explained. by looking at the effect of some protein kinases on these various impacts of cardiac cell physiology. We see it depicted nicely in this diagram.

So epinephrine and norepinephrine are binding to beta adrenergic receptors, and via a G-protein coupled mechanism are activating adenylal cyclase, which in turn elevates cyclic AMP levels in the cell, which activates protein kinases. Once the protein kinases are active, then they have five impacts on these various intracellular aspects of cardiac cell physiology. They increase the speed at which the L-type calcium channels open. We're certainly familiar with those at this point. They increase the speed at which the ryanodine receptor channels in the sarcoplasmic reticulum are opening and releasing calcium.

They increase the thin filament activation by... calcium of troponin, they enhance cross-bridge cycling and thick and thin filament sliding and therefore force generation. And then lastly, but very importantly, they increase the speed at which the calcium is transported back into the sarcoplasmic reticulum.

All these factors then contribute to both the increased stroke volume and the increased speed at which the generation of force and therefore the ejection of blood in the stroke volume takes place. place. Lastly, the third factor that we just mentioned that controls the amount of blood that's ejected with each stroke volume is the so-called afterload.

In other words, that would be the pressure that's... found in the arteries that the left and right ventricles are pumping blood into. So generally, this has a minimal influence on cardiac output because it's typically It's typically constant. It typically changes very little as a result of some physiological factors, the ability of the smooth muscle found in the blood vessels to constrict and dilate.

But we do see in some cases where a person is suffering from chronically high blood pressure, this does have an overall negative impact on the cardiac output. It can be very damaging physiologically. But for the most part, it has... very minimal impacts on the cardiac output in a healthy individual.

So we close this discussion by summarizing the impacts that we just went over related to cardiac output. So if we increase the end diastolic volume via the Frank Starling mechanism of the heart, we increase the stroke volume and increase the cardiac output. If we increase the sympathetic activity and therefore increase the sympathetic activity in the nervous system, we increase the sympathetic activity in nerves going to the heart, we both increase the stroke volume and we increase the heart rate. If we increase plasma epinephrine, then we increase the stroke volume and increase the heart rate via the identical mechanisms that we just talked about to what we see if we actually increase the activity of the sympathetic nerves. And of course, if we decrease the parasympathetic activity of the nerves that are headed to the heart, mostly the atria, then we increase the heart rate.

rate, we see that we don't have any impact on the overall stroke volume because those parasympathetic nerves, as you remember, are going to the atria, impacting the sinoatrial node, but they're not impacting the ventricles.

Transcript for:Understanding the Cardiac Cycle and Physiology

Transcript for:
Understanding the Cardiac Cycle and Physiology