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.