Inotropy: Definition, Regulation and Effects – Cardiac Mechanics

by Thad Wilson, PhD

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    00:01 Inotropy is going to be the force at which a contraction occurs.

    00:06 This is a length independent activation, meaning that it doesn't matter how much stretch the cardiac myocyte is under.

    00:13 It’s how much force it's going to be able to contract.

    00:17 In this case, it depends upon the preload, but it is independent of preload in many ways.

    00:24 The stroke volume will increase, as you increase the force of contraction or inotropy.

    00:34 So, what are the big factors that affect inotropy? There are four.

    00:38 The first of which is sympathetic activation.

    00:43 The more of a fight or flight response you have, the greater the contraction of each individual heartbeat.

    00:51 You notice, or remember from previous lectures, that you also increase the beat frequency.

    00:57 But in this case, you increase the strength of the contraction.

    01:01 Circulating catecholamines is the second reason.

    01:04 And again, a catecholamine is a blood-borne either epinephrine or norepinephrine.

    01:10 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.

    01:22 The other two factors: One is an increase in heart rate.

    01:26 And this is something called a Bowditch effect.

    01:28 These particular effects, as the heart beats more and more frequently, it gets a little bit stronger in its contraction.

    01:36 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.

    01:44 The last thing that affects inotropy is going to be the afterload.

    01:50 You have to overcome a certain afterload to be able to push out a particular amount of blood.

    01:58 And if afterload increases, inotropy will increase to overcome that afterload because, remember, you have these interrelated effects.

    02:12 So, let’s look at – I mean, inotropy affects ventricular function.

    02:16 So, this curve, / we’ve seen a couple of times now, we're just going to talk you through how it affects inotropy.

    02:23 We have left ventricular and diastolic pressure here on the x-axis and we have stroke volume here on the y-axis.

    02:30 If we have an increase in inotropy, that is going to allow us to contract harder.

    02:37 A decrease in inotropy, you contract less hard.

    02:42 So, let's go through first an increase in inotropy.

    02:45 So, that is going from A to C.

    02:49 In this case, you can see that the whole curve shifts up to a new level.

    02:53 Therefore, at a lower end-diastolic pressure, you can generate more stroke volume because you are contracting harder.

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

    03:08 Therefore, even at a higher left ventricular end-diastolic pressure, you’re not going to be able to garner as much stroke volume.

    03:15 This increase in inotropy also involves an increase in ejection velocity.

    03:21 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.

    03:33 Another way to quantify this increase in inotropy is the development of pressure.

    03:40 The faster you can develop pressure, the more inotropy you have.

    03:45 So, oftentimes, that is another way we look at inotropy.

    03:49 And we quantify by this dP/dT.

    03:54 dP is a change in pressure over dT, which is a change in time.

    04:00 The last way that we quantify that – we do this in the clinic quite a bit.

    04:05 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.

    04:21 If ejection fractions decrease, it is an index of a decrease in inotropy.

    04:28 So, let's think about what causes a muscle contraction in a cardiac myocyte.

    04:34 In this case, we have the release of norepinephrine from sympathetic nerve terminals.

    04:40 It will bind to beta-1 adrenergic receptors, which increase cAMP.

    04:46 cAMP will do two things for us.

    04:49 The first is, it allows for calcium to enter via L-type calcium channels.

    04:57 This calcium that enters also opens up calcium channels that are on the sarcoplasmic reticulum.

    05:03 And this will release even more calcium.

    05:06 So, this brings up an interesting concept, and that is cardiac myocytes use calcium-induced calcium release.

    05:16 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.

    05:28 Calcium induce, calcium release.

    05:31 The other thing that cAMP does is it phosphorylates a special protein called phospholamban.

    05:38 Phospholamban will help facilitate the calcium ATPase or the calcium pump to pump more calcium back into the SR or sarcoplasmic reticulum.

    05:50 That allows for the next contraction to be even greater.

    05:54 So, we have multiple processes engaged by the sympathetic nervous system to cause this effect to happen.

    06:02 The big point to remember here is the amount of calcium in the cytosol is very important.

    06:08 The more calcium you have in the cytosol, the greater the strength of contraction or the more inotropy.

    06:15 The less calcium you have, the lower the inotropy.

    06:18 So, strength of contraction is always variable on the amount of calcium you have present.

    06:25 The more calcium, the greater the contraction.

    06:27 Less calcium, the less contraction.

    06:30 That's why sympathetic stimulation releases calcium.

    06:33 Why? To get an increased strength of contraction.

    06:37 So, now, let's look at inotropy on everybody's favorite pressure-volume loops.

    06:42 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.

    06:57 Here, let's first take an increase in inotropy.

    07:03 An increased inotropy is an increased strength of contraction.

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

    07:14 We’ve moved it upwards and a little bit to the left.

    07:19 This upward shift allows us to use a new maximum curve to work on.

    07:25 The end result is that you will have a lower end-systolic volume and a greater stroke volume.

    07:33 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.

    07:44 That means that per stroke, you won't get as much stroke volume per stroke.

    07:53 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. Increase dP/dt
    4. Increase EF
    5. Decrease preload
    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
    1. An increase in sympathetic nervous system stimulation
    2. A decrease in circulating catecholamines
    3. A decrease in heart rate
    4. A decrease in afterload
    5. Parasympathetic nervous system stimulation
    1. Calcium
    2. Sodium
    3. Potassium
    4. Chloride
    5. Magnesium

    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.