Greetings, today we want to continue our discussion of the cardiovascular system, In particular we want to think about how the heart adjust its output of blood to match the needs of the body in general. There many objectives that we want to consider. The first is to define and calculate the injection fraction of the heart. Secondly, to discuss what's known as the Frank-Starling relationship. In terms of venous return, that is the blood coming back into the heart and its filling versus cardiac output. That is how much blood is actually being ejected from the heart to enter into the circulatory system. Third we want to explain the effects of the sympathetic nervous system on cardiac output. Okay, so what do we mean by cardiac performance or cardiac output? The cardiac output is the volume of blood that's pumped each minute. As you know from the last time when we met, the cardiac output is equal to stroke volume times heart rate. The heart rate is typically about 72 beats per minute. The stroke volume about 70 milliliters. So the cardiac output at rest is about 5 liters per minute. But we know that [cough], excuse me, individuals such as athletes can have a much lower heart rate. They can have a very high parasympathetic tone. By having a high parasympathetic tone they have lower heart rate. But they still have, at rest, a cardiac output of five liters per minute. This means that the heart had to adjust the stroke volume. The stroke volume increases in a well trained athlete. An individual who has a heart rate of 50 milliliters per minute, beats per minute, and has a cardiac output of 5 liters per minute will then have a stroke volume of 100 milliliters. The other way of thinking about the heart and its function, is to think about the ejection volume, or the ejection fraction. This is calculate by the stroke volume divided by the end diastolic volume, that is by the volume at the end of diastole when the ventricles are full. That is EJ = SV/EDV X 100. This gives us the percentage of blood that's pumped from the filled ventricle per beat. [COUGH] Excuse me. Typically, when we have a normal heart, the ejection fraction is anywhere from 50 to maybe 70 or 75%. But in a weak heart, where the heart has gained size but not gained stength, then those hearts will have an ejection fraction that's much lower. Let's look at what's happening. We can consider this by looking at our pressure volume loops. what we have here on the Y axis is pressure, and on the X axis is volume. The volume is increasing in this direction. We have one heart, that's heart A. Let's fill it with more blood as it goes through diastole. This shifts Heart A to Heart B by simply increasing the end diastolic volume. That's what's here on the x axis. To shift the heart volume in heart A, wesimply add more volume to it. As we fill it more you'll notice that it started with a systolic pressure of 100, but now the filled heart, a heart that has more blood within the ventricle, can generate up to 180 mmHg. It is now generating 180 mmHg pressure. That change occured by simply filling the same heart with more blood. We were able to get a better contraction, better force from that particular heart. We now have a higher systolic pressure. That's an advantage. That's why the heart will in fact, meet their increased demand by increasing volume within the system, that is the filling of the heart. In this particular case, the stroke volume of the two loops, heart A and Heart B, were kept at 40 milliliters. What if we calculate the ejection fraction from loop A, that is the heart at rest before we started to fill it with more blood. What we find is that 40 divided by 90 gives us an ejection fraction of 44%. But what about the injection fraction from loop B? It's the same heart A but we've added more volume. There is more blood in the ventricle. The stroke volume remains at 40. Now when 40 is divided by 140, the end diastolic volume, the ejection fraction is changed. Now that heart has only about 28% ejection fraction. So although it can give us more pressure, it can generate more pressure, the heart is, in fact, not as efficient at doing so. Under normal conditions, [COUGH] excuse me, under normal conditions when the heart is filling with more volume, the stroke volume is also increasing. This is due to the Frank Starling relationship. Remember we said that the heart is not able to recruit muscle fibers like skeletal muscle to generate more tension. As the heart is pumping, it's using all of the muscle fibers. They're all connected through gap junctions. They're synchronously contracting, pumping. So we can't recruit more fibers to generate more power. Instead, when we stretch the heart, we stretch the myocytes, then they will give a better contraction. This we said was due to the differences in the molecular arrangements within the fibers themselves. This is known as the Frank-Starling effect. Effectively what it's says is that the volume coming in to a normal heart is the volume that will be ejected by that normal heart. Let's consider this particular figure. On the x axis, there is the left ventricular end diastolic volume, or EDV. And on the y axis is the ejection volume. As you know, that's the stroke volume. So we have stroke volume versus the end diastolic volume. If we start our heart here at rest, it has an end diastolic volume of 100. Then as we fill this normal heart, we fill it and move it to an End Diastolic Volume of a 150. Notice that we now have moved the stroke volume. It has increased. The stroke volume has gotten bigger. So when the heart had an end diastolic volume of a 100, we have a stroke volume that was about 70. But that same heart with end diastolic volume of 150 milliliters, will give us a stroke volume that's now at about 90 mL. So, we can increase the stroke volume by filling the heart. This filling of the heart is referred to as venous return. It's also referred to as preload. Preload increases the ability of the heart to eject blood. It's increasing it's contraction and it's power. It's able to generate more force by stretching the ventricles. The filling of the ventricles is called preload. Okay, so how does the body adjust preload? There's several mechanisms by which preload can be increased. That's what's noted here. The first is what's called the skeletal muscle pump. As an individual starts to run let's say, they are requiring more blood to be delivered to the muscles to deliver more oxygen to the contracting muscles. The contraction of the muscle itself is squeezing against the veins that are within that tissue. And as it squeezes against the veins, it is helping to propel the blood out of the tissue, and back towards the heart. That simply, the local effect, and it is called the skeletal muscle pump. The second way that we can increase the return of blood to the heart or increase venous return, is what's known as the respiratory pump. So again as we're running and we're taking bigger breaths, then the expansion of the thorax, as you're taking a larger breath, decreases the pressure that's around the heart. That means that the heart can actually expand easier, and so the blood then can flow back into the heart faster. This inspiration, taking in a big breath, like this, lowers the thoracic pressure. Fourth, and I'm gonna skip three. We'll come back to it in a second. fourth, we have what's called vasoconstriction. So this is the smooth muscle of the blood vessels on the arterial side. These constrict when we have sympathetic drive. This constriction is due to activity of the alpha one andrenergic receptors. As these smooth muscle cells constract, they force the blood from the arterial side to the venous side of the circulation. This then, augments the return of blood to the heart. In addition, we have smooth muscle that's located along the long axis of the veins. This smooth muscle also can contract. As it contracts due to the sympathetic drive, then we again augment the flow of blood back to the heart. So vasoconstriction or sympathetic drive will increase venous return. It aids in the filling of the heart. What about this number three? This is called an increase in blood volume due to doping. Doping is a concept where an individual will take blood or donate blood, takes the blood from his own circulatory system. Let's say a half a liter, and he stores it. Then, just before a race, that blood is given back to the individual. The individual has five liters of blood within his circulation and he's getting back another half a liter to the circulation. He now has onboard five and a half liters of blood. This obviously increases his ability to carry oxygen. There's more red blood cells within the circulatory system. It also increases the volume within the circulatory system. So we have more volume then that can be delivered to the heart. This aids then in the delivery of blood to the tissues. It is illegal. it is illegal partly because it gives an unfair advantage to these individuals in an athletic event. But most importantly by giving this extra blood back to the individual, we're increasing the viscosity of the blood. You're changing the pressure within the system by giving more blood cells to the body. What happens when the individual becomes dehydrated?. They lose fluid during the athletic event through sweating. This individual's blood actually has a higher hematocrit. It has more blood cells per unit volume. Under those conditions the viscosity increases. This is actually harder on the heart. It's more work for the heart to push through a more viscous blood and can be quite dangerous. It is illegal. The last system that we're gonna consider is that the cardiac myocytes themselves are sensitive to certain chemicals. These chemicals are called ionotropic agents. An ionotropic agent is an agent that can increase the contractility of the muscle cells themselves, or the muscle fibers themselves. That's what's shown here. So here we have, again, the left ventricle end diastolic volume on the x axis. The ejection volume, or stroke volume, is on the y axis. Under the resting state where we have normal Individual when all we've done is increase the volume to this individual. As we know, by increasing the volume, we increase stroke volume. So if we increase end diastolic volume, deliver, preload to the heart, we increase stroke volume. But let's keep the end diastolic volume constant at 100 mL. So, we're sitting here. Now, we'll give an ionotropic agent to the individual. Ionotropic agents are things such as catecholamines. Norepinephrine and epinephrine are ionotropic agents. If we give a sympathetic discharge, or norepinephrine, to this individual, what happens is that the heart at that exact same end diastolic volume, can give a better squeeze. That means it ejects more blood. So we move the stroke volume from something like 35 mL to 70 mL. We've greatly improved the ability of the heart to eject the blood. That occured by changing the contractility of the muscle cells themselves. This change in contractility is due to multiple effects. These occur at the level of the myofibrils themselves, and also the sarcoplasmic reticulum, as well as within the plasma membrane itself. The entire cell becomes more sensitive to calcium. By doing so, we're able to have a faster off-rate and on-rate for calcium. Contraction is actually improved. So sympathetic stimulation is a way the heart can affect not only venous return. Wherein it promotes constriction of blood vessels and so by doing moves blood back to the heart faster. It ialso increases the contractility of the heart itself, of the myocyte itself. The contraction of the myocyte is more forceful. Then lastly, as you know, it increases heart rate. So cardiac output equals stroke value times heart rate. The sympathetic nervous system not only increases heart rate, but it also can increase stroke volume, and therefore can increase cardiac output. Okay, so what's our key concepts then? The general concepts are first, that the volume of the blood which is ejected with each beat is called the stroke volume. Second, the sum of the stroke volumes ejected in one minute is the cardiac output. Third, the ejection fraction is the percentage of blood which is pumped from the heart in each beat. Fourth, cardiac output increases with increased filling of the ventricles. This is referred to as venous return, and also as preload. The cardiac output can increase with an increase in sympathetic stimulation or by giving an ionotophc agent to the heart. All right, so see you next time.
