Inotropy is going to be the force
at which a contraction occurs.
This is a length independent activation,
meaning that it doesn't matter
how much stretch the
cardiac myocyte is under.
It’s how much force it's going
to be able to contract.
In this case,
it depends upon the preload,
but it is independent of preload in many ways.
The stroke volume will increase,
as you increase the force of contraction or inotropy.
So, what are the big factors that affect inotropy?
There are four.
The first of which is sympathetic activation.
The more of a fight or flight response you have,
the greater the contraction
of each individual heartbeat.
or remember from previous lectures,
that you also increase the beat frequency.
But in this case,
you increase the strength of the contraction.
Circulating catecholamines is the second reason.
a catecholamine is a blood-borne
either epinephrine or norepinephrine.
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.
The other two factors:
One is an increase in heart rate.
And this is something called a Bowditch effect.
These particular effects,
as the heart beats more and more frequently,
it gets a little bit stronger in its contraction.
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.
The last thing that affects inotropy
is going to be the afterload.
You have to overcome a certain afterload
to be able to push out
a particular amount of blood.
And if afterload increases,
inotropy will increase to overcome that afterload
because, remember, you have
these interrelated effects.
So, let’s look at –
I mean, inotropy affects ventricular function.
So, this curve,
/ we’ve seen a couple of times now,
we're just going to talk you
through how it affects inotropy.
We have left ventricular and diastolic
pressure here on the x-axis
and we have stroke volume here on the y-axis.
If we have an increase in inotropy,
that is going to allow us to contract harder.
A decrease in inotropy,
you contract less hard.
So, let's go through first an increase in inotropy.
So, that is going from A to C.
In this case,
you can see that the whole curve
shifts up to a new level.
Therefore, at a lower end-diastolic pressure,
you can generate more stroke volume
because you are contracting harder.
When you go from A to B,
you’re contracting less hard.
even at a higher left ventricular end-diastolic pressure,
you’re not going to be able to garner
as much stroke volume.
This increase in inotropy
also involves an increase in ejection velocity.
In this man,
it’s a nice thing to have happened
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.
Another way to quantify this increase in
inotropy is the development of pressure.
The faster you can develop pressure,
the more inotropy you have.
that is another way we look at inotropy.
And we quantify by this dP/dT.
dP is a change in pressure
over dT, which is a change in time.
The last way that we quantify that –
we do this in the clinic quite a bit.
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.
If ejection fractions decrease,
it is an index of a decrease in inotropy.
So, let's think about what causes a
muscle contraction in a cardiac myocyte.
In this case,
we have the release of norepinephrine
from sympathetic nerve terminals.
It will bind to beta-1 adrenergic receptors,
which increase cAMP.
cAMP will do two things for us.
The first is,
it allows for calcium to enter
via L-type calcium channels.
This calcium that enters also opens up calcium channels
that are on the sarcoplasmic reticulum.
And this will release even more calcium.
So, this brings up an interesting concept,
and that is
cardiac myocytes use calcium-induced calcium release.
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.
Calcium induce, calcium release.
The other thing that cAMP does
is it phosphorylates a special protein
Phospholamban will help facilitate the calcium ATPase
or the calcium pump
to pump more calcium
back into the SR or sarcoplasmic reticulum.
That allows for the next
contraction to be even greater.
So, we have multiple processes
engaged by the sympathetic nervous system
to cause this effect to happen.
The big point to remember here
is the amount of calcium in
the cytosol is very important.
The more calcium you have in the cytosol,
the greater the strength of contraction
or the more inotropy.
The less calcium you have,
the lower the inotropy.
So, strength of contraction is always variable
on the amount of calcium you have present.
The more calcium,
the greater the contraction.
the less contraction.
That's why sympathetic
stimulation releases calcium.
To get an increased strength of contraction.
So, now, let's look at inotropy on everybody's
favorite pressure-volume loops.
If we put our parameters out
for our maximal and minimal,
we put in our normal pressure-volume loop
where we get ventricular filling,
ejection and isovolumic relaxation.
Here, let's first take an increase in inotropy.
An increased inotropy is
an increased strength of contraction.
You notice this is the first time
that we've altered a pressure-volume curve,
in which we’ve altered that maximal value.
We’ve moved it upwards
and a little bit to the left.
This upward shift
allows us to use a new maximum curve to work on.
The end result is that
you will have a lower end-systolic volume
and a greater stroke volume.
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.
That means that per stroke,
you won't get as much
stroke volume per stroke.
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.