Inotropy: Definition, Regulation and Effects – Cardiac Mechanics

by Thad Wilson, PhD

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    00:01 Inotropy.

    00:03 Inotropy is going to be the force at which a contraction occurs.

    00:08 This is a length independent activation, meaning that it doesn't matter how much stretch the cardiac myocyte is under.

    00:15 It’s how much force it's going to be able to contract.

    00:19 In this case, it depends upon the preload, but it is independent of preload in many ways.

    00:26 The stroke volume will increase, as you increase the force of contraction or inotropy.

    00:36 So, what are the big factors that affect inotropy? There are four.

    00:40 The first of which is sympathetic activation.

    00:45 The more of a fight or flight response you have, the greater the contraction of each individual heartbeat.

    00:53 You notice, or remember from previous lectures, that you also increase the beat frequency.

    00:59 But in this case, you increase the strength of the contraction.

    01:03 Circulating catecholamines is the second reason.

    01:06 And again, a catecholamine is a blood-borne either epinephrine or norepinephrine.

    01:12 It’s usually produced from the adrenal medulla and that will be traveling around to the circulation, bind to the beta-1 adrenergic receptors to increase ventricular inotropy.

    01:24 The other two factors: One is an increase in heart rate.

    01:28 And this is something called a Bowditch effect.

    01:30 These particular effects, as the heart beats more and more frequently, it gets a little bit stronger in its contraction.

    01:38 And this process, we’ll get into a little bit more with skeletal muscle, but in this case, know that the principle is the same.

    01:46 The last thing that affects inotropy is going to be the afterload.

    01:52 You have to overcome a certain afterload to be able to push out a particular amount of blood.

    02:00 And if afterload increases, inotropy will increase to overcome that afterload because, remember, you have these interrelated effects.

    02:14 So, let’s look at – I mean, inotropy affects ventricular function.

    02:18 So, this curve, / we’ve seen a couple of times now, we're just going to talk you through how it affects inotropy.

    02:25 We have left ventricular and diastolic pressure here on the x-axis and we have stroke volume here on the y-axis.

    02:32 If we have an increase in inotropy, that is going to allow us to contract harder.

    02:39 A decrease in inotropy, you contract less hard.

    02:44 So, let's go through first an increase in inotropy.

    02:47 So, that is going from A to C.

    02:51 In this case, you can see that the whole curve shifts up to a new level.

    02:55 Therefore, at a lower end-diastolic pressure, you can generate more stroke volume because you are contracting harder.

    03:05 When you go from A to B, you’re contracting less hard.

    03:10 Therefore, even at a higher left ventricular end-diastolic pressure, you’re not going to be able to garner as much stroke volume.

    03:17 This increase in inotropy also involves an increase in ejection velocity.

    03:23 In this man, it’s a nice thing to have happened because sometimes when you have a decrease in left ventricular end-systolic volume, there is also a need to be able to push that blood out very rapidly.

    03:35 Another way to quantify this increase in inotropy is the development of pressure.

    03:42 The faster you can develop pressure, the more inotropy you have.

    03:47 So, oftentimes, that is another way we look at inotropy.

    03:51 And we quantify by this dP/dT.

    03:56 dP is a change in pressure over dT, which is a change in time.

    04:02 The last way that we quantify that – we do this in the clinic quite a bit.

    04:07 If you look at someone's ejection fraction – and ejection fraction is, per amount of stroke volume, what was the end-diastolic volume? If ejection fractions increase, that is an increase in inotropy.

    04:23 If ejection fractions decrease, it is an index of a decrease in inotropy.

    04:30 So, let's think about what causes a muscle contraction in a cardiac myocyte.

    04:36 In this case, we have the release of norepinephrine from sympathetic nerve terminals.

    04:42 It will bind to beta-1 adrenergic receptors, which increase cAMP.

    04:48 cAMP will do two things for us.

    04:51 The first is, it allows for calcium to enter via L-type calcium channels.

    04:59 This calcium that enters also opens up calcium channels that are on the sarcoplasmic reticulum.

    05:05 And this will release even more calcium.

    05:08 So, this brings up an interesting concept, and that is cardiac myocytes use calcium-induced calcium release.

    05:18 The calcium induced is the calcium going from outside the cell inside the cell, and then the calcium release is from the sarcoplasmic reticulum into the cytosol.

    05:30 Calcium induce, calcium release.

    05:33 The other thing that cAMP does is it phosphorylates a special protein called phospholamban.

    05:40 Phospholamban will help facilitate the calcium ATPase or the calcium pump to pump more calcium back into the SR or sarcoplasmic reticulum.

    05:52 That allows for the next contraction to be even greater.

    05:56 So, we have multiple processes engaged by the sympathetic nervous system to cause this effect to happen.

    06:04 The big point to remember here is the amount of calcium in the cytosol is very important.

    06:10 The more calcium you have in the cytosol, the greater the strength of contraction or the more inotropy.

    06:17 The less calcium you have, the lower the inotropy.

    06:20 So, strength of contraction is always variable on the amount of calcium you have present.

    06:27 The more calcium, the greater the contraction.

    06:29 Less calcium, the less contraction.

    06:32 That's why sympathetic stimulation releases calcium.

    06:35 Why? To get an increased strength of contraction.

    06:39 So, now, let's look at inotropy on everybody's favorite pressure-volume loops.

    06:44 If we put our parameters out for our maximal and minimal, we put in our normal pressure-volume loop where we get ventricular filling, isovolumic contraction, ejection and isovolumic relaxation.

    06:59 Here, let's first take an increase in inotropy.

    07:05 An increased inotropy is an increased strength of contraction.

    07:09 You notice this is the first time that we've altered a pressure-volume curve, in which we’ve altered that maximal value.

    07:16 We’ve moved it upwards and a little bit to the left.

    07:21 This upward shift allows us to use a new maximum curve to work on.

    07:27 The end result is that you will have a lower end-systolic volume and a greater stroke volume.

    07:35 If you have a decrease in inotropy, that is a lower strength of contraction, you’ll see that that line will shift downwards and to the right.

    07:46 That means that per stroke, you won't get as much stroke volume per stroke.

    07:55 Interestingly, when you're measuring this, it looks like the end-systolic volume is elevated, but this is simply an artifact of not pushing out as much blood per stroke.

    About the Lecture

    The lecture Inotropy: Definition, Regulation and Effects – Cardiac Mechanics by Thad Wilson, PhD is from the course Cardiac Physiology.

    Included Quiz Questions

    1. Decreases stroke volume
    2. Increases stroke volume
    3. Does not change stroke volume
    1. Increased preload
    2. Increased stroke volume
    3. Increased rate of ventricular pressure development
    4. Increased ejection velocity
    1. L-type calcium channel
    2. T-type calcium channel
    3. R-type calcium channel
    4. N-type calcium channel
    5. P-type calcium channel

    Author of lecture Inotropy: Definition, Regulation and Effects – Cardiac Mechanics

     Thad Wilson, PhD

    Thad Wilson, PhD

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    Very good description of Cardiac Mechanics
    By Timothy B. on 12. January 2018 for Inotropy: Definition, Regulation and Effects – Cardiac Mechanics

    The explanation is short and simple. Very easy to understand, it allows me the time to think about what is happening.