Pharmacologic agents: Drugs which increase cardiac contractility are called positive inotropic agents. Examples of these are dopamine, adrenalin and digoxin. Contractility describes the relative ability of the heart to eject a stroke volume (SV) at a given prevailing afterload (arterial pressure) and preload (end-diastolic. Cardiac contractility is the intrinsic ability of heart muscle to generate force and to shorten, autonomously of changes in heart rate (HR), preload or afterload.
So it turns out that, I guess, when I froze time at 9: And some of that calcium is, of course, binding to troponin C. And I'm just going to scatter some calcium randomly, so I really am not putting too much thought into exactly where it goes. But it's kind of throwing it out there.
And now our question is going to be how many myosin heads are actually working. And I'm going to circle the ones that are working in red. So this one is working because it's close to actin. And there's calcium on there, and it's the right polarity. But the next one over, this one, I'm not going to circle because it's the wrong polarity.
This one has calcium that's too far. It's on the wrong side. And this guy-- well, this guy actually would be circled because he's got calcium on the right-polarity actin.
This guy I would circle as well for the same reason. And these two I cannot circle because they're the wrong polarity. But this one I will circle. So we've got about 4 out of 20 that are working. And I could actually just rewrite that as 4 out of 20 works out to-- what?
So that's not great, but it's not awful, either. So to sum this up, at 9: Now that night, 9: I also headed out, went outside. And wanted to do one last little look around. And I encountered a scary animal, a scary beast, I would even say.
And this animal had four legs-- and let's see if you can recognize it-- had a striped tail and a striped body. And this horrible, horrible little creature is none other than a raccoon. So this is my little raccoon with a ugly little face. And this raccoon, like many raccoons do, scared me.
And you should know, I do actually in fact have a fear of raccoons. And so this was a very scary event for me. I shrieked, and I was not too happy. So what was going on in my heart at that time? Let's actually do a little cut-paste job. All right, so now I'm basically just going to try to cut and paste some of this, and I'll erase the parts that are not relevant.
So I've got something like that. And let me just quickly erase the parts that I know I'm not going to want. So let's start there. I've got my sympathetic nerves that are now going to be going crazy. I'm going to just draw a giant arrow because they are going to be driving a message down there saying, hey, this raccoon is awful and scary. Let's just get lots and lots of neurotransmitter released. So they're going to just release tons and tons of neurotransmitter. And that is an important issue.
This is how signals get passed. And so, of course, now all of my receptors are jamming that signal. And of course, that signal means that calcium is going to flood my cell. All of a sudden, I have much more calcium in my cell than I used to, tons and tons of calcium.
And in fact we know that this is the key way that our nerves are able to communicate a message. They basically help by sending ions into cells. So now our cell is jam-packed full of calcium. And so now I can just kind of scatter calcium everywhere, just kind of sprinkle it all over the place. And let's see what happens now. So I've got calcium everywhere. And same question as before-- how many myosin heads, rather, are going to be working for us. So let's just circle the ones that are working for us.
We still have a few that are not going to be working because they're blocked by the wrong-polarity actin. But these are actually now all recruited. All of these are. And on the other side, I've got some recruitment over here.
So I've got lots and lots of myosin heads recruited. I've got-- let's see if I can count it up-- 5, 10, 11, So I've got 12 out of I'm going to make a little bit of space on our canvas now. But just kind of think about that, the fact that at 9: So what does that mean exactly? How can we put that together in an image that we can kind of remember and think about and make sense of?
So for this part, I think it would be helpful to go back to our pressure-volume curves. So we've got this idea that at the end of systole, we have a relationship called the end-systolic pressure-volume relationship. I'm actually going to draw it out here. This is a sketch of our end-systolic pressure-volume relationship. And we know-- and yellow will be our 9: Let's just kind of keep that in mind. This is what was happening in the morning as I was relaxed.
So if I was-- let's just take a spot here, and I could take any spot. I'm just choosing it randomly. And let's say this is the volume at that spot. And if I fill it in with blood, it would look like that. And at this point, we've got our workers. Remember, our workers represent how much force of contraction there is.
So our workers are yanking this way and that on this rope. And our worker-- I'm just going to quickly sketch out-- maybe looks like that. And we've got another worker down here-- long arms, apparently.
And if I was to look at my workers' faces-- because I've drawn the faces very, very small, it's hard to see them-- they're yanking. It's not like they're-- they're not lazy. They're not just standing there. Just to make it kind of the same as the other one. And I'm actually going to just kind of sketch higher-- maybe something like this. So at that same volume, it would basically look like this. And I've going to try to draw the exact same volume so you believe me. This is, let's say, the same volume-- about the same, anyway.
And here, let's fill it up with blood. We've got our two workers doing kind of the same thing. We've got workers yanking on this left ventricle. And these workers are working much harder. Changes in inotropy are an important feature of cardiac muscle because unlike skeletal muscle, cardiac muscle cannot modulate its force generation through changes in motor nerve activity and motor unit recruitment.
When heart muscle contracts, all muscle fibers are activated and the only mechanisms that can alter force generation are changes in fiber length preload ; length-dependent activation and changes in inotropy length-independent activation. The influence of inotropic changes in force generation is clearly demonstrated by use of length-tension diagrams in which increased inotropy results increases active tension at a fixed preload. Furthermore, the inotropic property of cardiac muscle is displayed in the force-velocity relationship as a change in V max ; that is, a change in the maximal velocity of fiber shortening at zero afterload.
Because of these changes in the mechanical properties of contracting cardiac muscle, an increase in inotropy leads to an increase in ventricular stroke volume. By altering the rate of ventricular pressure development, the rate of ventricular ejection into the aorta i. A decrease in inotropy shifts the Frank-Starling curve downward point A to B in the figure. This is what occurs, for example, when there is a loss in ventricular inotropy during certain types of heart failure.
Once a Frank-Starling curve shifts in response to an altered inotropic state, changes in ventricular filling will alter SV by moving either up or down the new Frank-Starling curve.
In this figure, the control loop has an end-diastolic volume of mL and an end-systolic volume of 50 mL. The width of the loop end-diastolic minus end-systolic volume is the stroke volume 70 mL. When inotropy is increased at constant arterial pressure and heart rate SV increases, which reduces the end-systolic volume to 20 mL. This is accompanied by a secondary reduction in ventricular end-diastolic volume to mL and pressure because when the SV is increased the ventricle contains less residual blood volume after ejection decreased end-systolic volume , which can be added to the incoming venous return during filling.
Therefore, ventricular filling end-diastolic volume is reduced. Changes in inotropy produce significant changes in ejection fraction EF, calculated as stroke volume divided by end-diastolic volume. In the previous figure, the control EF is 0. Therefore, increasing inotropy leads to an increase in EF.
Inotropy Cardiac contractility can be defined as the tension developed and velocity of shortening (i.e., the “strength” of contraction) of myocardial fibers at a given. Myocardial contractility represents the innate ability of the heart muscle (cardiac muscle or myocardium) to contract. The ability to produce changes in force. Myocardial contractility is the ability of the heart to increase force of contraction, determined by the strength of the actomyosin filament interaction, which, in turn.