Would you give your right arm to protect your heart? (22 March 2011)


Uploaded by UCLLHL on 23.03.2011

Transcript:
>> Thank you very much for that introduction.
I'm just waiting for the alarm to go and it happened
when I went from there to my next slide.
And I thought I'd start this talk by giving some numbers.
We're so used to huge numbers these days
but this so-called epidemiological slide sets the
scene for why people like myself and others are involved
in cardiovascular research.
If you look at this enormous figure here, that's 6 billion,
that's the worldwide population
which I'm reliably told this morning by October this year,
we'll be just close to 7 million.
Of that, the total number of deaths per year are 54 million.
So from 6 billion, you get 54 million deaths per year.
And then more importantly from a cardiovascular point of view,
you can see that 31 percent of those deaths are someway related
to the heart, be it coronary artery disease
or cardiovascular such as stroke.
To put this in context of course, it's important
to appreciate that there are other very important diseases
such as AIDS, tuberculosis, and malaria.
But you can clearly see that they are in a minority compared
to cardiovascular disease.
So, there is something that we have to work on continuously
to find ways to reduce this significant number of deaths.
Well, what has led to the potential for men
to suffer a heart attack?
If you look through the last 200,000 years when men started
to walk upright, you can see that probably he died
of either saber tooth tiger bites or some infection.
But just in the last 100 years or so, that's the problem.
And you can clearly see that that problem on the right is--
leads to a potential to suffer heart attacks.
One could also argue that if you look at this guy here
who is also obese and pressing his finger on a telephone,
on a mobile phone, he's evolving a large thumb
because of all the texting he is doing.
But the message here is quite simple,
exercise is very important and obesity and overweight leads
to heart attack and diabetes.
So what is a heart attack and how is it caused?
Recently, a heart attack is caused if you got--
these are the coronary arteries supplying blood to the heart,
if you have a blockage here as you will see here due
to a plaque and a blood clot, you will get distal
to that muscle that dies.
And a nice way to look at this is to look at a normal heart
and you see that the heart is made up of trillions of cells
that beat away very easily here.
And what happens next.
And this is showing you a dying cell.
If I can get this movie going.
And so from a beating cell to a dying cell,
you can see that cell shrinks and dies and folds up
and that's happening during the course of a heart attack.
So we're gonna keep these cells in this condition here
for as long as possible.
Let me show you another movie 'cause this summarizes this
quite well.
This is a movie taken inside a coronary artery,
an imaginary coronary artery.
Now the blood is flowing towards you
and you can see the blood is made up of white blood cells,
red blood cells which carry oxygen
and these [inaudible] things called platelets
which are involved in blood clotting.
And as the bloods flow towards you, underneath here
over many years is a build up of plaque
and therefore these white blood cells will dive underneath
to investigate what's going on.
And you can see they'll move in there
and you'll get slowly this build up of plaque and cholesterol
which will take a number of years,
and you can see it building up here.
And all of a sudden, it will become like a volcano
and suddenly it erupts.
And you can see here this is what's happening now,
it's erupting with the leaking of blood, platelets at most run
like mad, crazy to get sticking to this blood clot
and you'll see a mesh and a clot occurring,
blocking off this whole artery in a few minutes.
And that is what is causing a heart attack.
To show you this in a real context,
look at this horrible picture.
This is a picture of a blood clot as in the same principle,
burst through from underneath the plaque, it ruptured
and that's gonna block that coronary artery.
So, the consequences of blocking of the coronary artery
by blood clot is what?
Well, simply it's a heart attack or myocardial infarction.
And you can see here, this is a myocardial infarction
as a consequence of blocking
by a blood clot blocking the flow to the heart.
Now, what can be done
when someone is having a myocardial infarction?
Well, there's a number of things you can do.
These are the three practical things
that occur on a daily basis.
At all major hospitals you can have the use
of clot busting drugs, the use
of something called primary angioplasty
which I will discuss with you in a minute.
As well as you can have
or undertake coronary artery bypass surgery.
And then I want to talk about some of the adaptive changes
that occur in the myocardial or in the heart
and I'll come back to that shortly.
Now let's look at what are clot busting drugs.
These are drugs that dissolve that blood clot
that I showed you earlier.
So, here's an example of an X-ray, an autoradiogram
of a 49-year-old male who has had 3 hours
after having a chest pain and you can see it quite clearly
that that position there is where his blood clot is.
This should be open it should--
blood should be flowing to the distal ends
of the heart quite freely than not.
If you give that patient a thrombolytic, in other words,
a clot-busting drug, you can see quite clearly that you've opened
up that artery and blood will flow.
But that takes about 35 minutes.
When you give a blood caused clogging, a clog-busting drug,
it's like an ice cream that melts.
It's not instantaneous, it takes a little time.
And the meantime, some of the muscle is dying
but eventually you will open up that artery
and blood will flow freely.
What about this primary angioplasty?
Well, what is primary angioplasty?
Well, here's a good friend and colleague of mine,
Dr. Malcolm Walker in the cath lab at the heart hospital
and he's putting a wire down the femoral artery of the patient
and he's going to insert that over the blood clot
and he's gonna blow up a balloon, remove the blood clot,
it's like Dyno-Rod and he's gonna remove the blood clot
and blood will flow freely
and then he's gonna put something called a stent,
which is basically a scaffold
which will keep that artery open.
And this is-- the whole process of this is primary angioplasty
and this happens to a patient who is having a heart attack,
gets rushed at the hospital, and this occurs.
Just to show you some old pretty pictures to make the point,
you can see here quite clearly, I hope you can, that that is
where the blood clot is.
It's something obscuring the flow of blood
down that coronary artery.
So what he will do is you put a guidewire into that artery
to know where it's sitting, he'll inflate a balloon
and [inaudible], that will be opened and blood will flow down.
To show you this in more graphic detail,
that's where the blood clot is.
I'll try and point this.
You can see this area distal
to the heart should be having blood flowing.
It's not, it's starting to die
because it is not getting any flow to the heart,
the muscle needs that blood.
What happens is in goes the balloon, inflates
and again remarkably, you can see this lovely clear,
our patent artery and that's being--
receiving blood and hopefully and that's done quickly
and I mean quickly, I mean within minutes,
if not a very few hours, you can save a lot of muscle
and muscle then is saving life.
Sorry, I'm just trying to get out of this.
Right, now I want to get to the exciting part,
as far as I'm concerned.
This is what happens when you have a heart attack.
This is what you have to do, but we are amazingly fortunate
that the heart looks after itself to a certain extent,
and they are [inaudible] adaptive changes that occur
to the benefit of the heart.
You get what is called collateral flow developing
and you get something called preconditioning
which I'll come to in a minute.
Let's start with collateral flow,
what do I mean by collateral flow?
Well-- sorry, I forgot
to mention coronary artery bypass surgery.
I hope there're no surgeons in this room,
because they will kill me.
But this is another way of perfusing
or returning blood flow to the heart
but simply this is open heart surgery and let's get
in a little closer, and you can see a lot of pipes and tubes,
and these tubes here basically are connecting to a blood--
a gas machine and they keep that oxygenated blood free
of the heart but the brain gets pumped with that blood.
>> So, what's happening here is--
this is so-called bypassing.
The heart is freed, it's quiescent.
It can then be worked on by the surgeon.
And you could see this is the really the principle of it all.
If you got a blood clot say
where these black marks are here, two blood clots
in this particular heart,
what the surgeon will do is you'll take an artery
from the leg or vein from the leg or a memory artery,
you'll connect it to the aorta
and you'll connect the distal part just past the blood clot
and that's called bypassing that particular clot
and you'll do the same with the vein.
You'll go from the low part of the aorta
to the distal end bypassing the clot bringing blood in.
So now, at last I am so excited.
I can get to the collateral flow bit.
What is collateral flow?
Well, this is a coronary vascular anatomy of a pig
and I'm sure you'll say, "Why is he showing you the coronary
vascular anatomy of a pig?"
Well, other than it's a beautiful picture,
if you had a blood clot, yeah, in that pig,
just say that position there, everything distal
to that would be not-- would not be supplied by blood
to that coronary artery and it would start to die.
Notice that there's no real blood coming
in from the other arteries to support it.
This is called an end artery system so that
if you have a blockage here, this will die.
There's no feed coming in to prop up that tissue.
Look at the difference between the pig and the dog
and it's quite clear to see
that a dog heart has a mass of collaterals.
So, if you could put a blockage,
blood clot in that particular branch or that artery,
you can see this area.
Well, I'm trying to do a circle, will become ischemic.
It's called-- well, not receiving flow,
will eventually die, but you can have blood flow coming
in from surrounding areas to prop up that tissue.
And you can keep that muscle viable and alive for much longer
than you could keep the pig heart muscle alive.
Well, what about the human?
'Cause all we're really interested in is the human.
Well, this is a human heart in the hands of a friend of mine,
did for a transplant, and you can see
that there's no much difference except the human heart is always
very, very fatty.
And please don't ask me why the human heart is very fat
at the end because the-- other than the obvious things,
nobody is really sure.
But let me go back to what a young adult,
this is from a postmortem of a young adult
and you can see here, does this remind you of any
of the other pictures I showed you?
Well, it should remind you of the pig,
is an endo artery system, you have a blockage here,
there's no feed coming in from collateral.
So therefore this muscle would die pretty quickly.
On the other hand, this is an old adult
with coronary artery disease, and reminds you of the dog.
It's got a massive developed collaterals.
So these collaterals develop as you get older due
to coronary artery disease.
So it's an adaptation that occurs to the benefit
of the old person with coronary artery disease.
You say, well, having coronary artery disease have no benefit
at all but you do get collaterals growing.
And just for interest, if you look down all the animals,
you can see the pig, the rabbit,
the baboon have surprisingly limited collateral flow,
whereas the cat and the dog have a bit more.
And for those of you who might have had guinea pigs
over the course of your life,
the guinea pig has just 100 percent collateral flow.
In other words, that tells you,
you can never give the guinea pig a heart attack.
It will always survive.
I've tried, believe in me, many, many years ago.
It will always survive because it has 100 percent
collateral flow.
It's remarkable why we're not learning from this.
Why the guinea pig is that, we don't know.
So, the young adult, and I'm looking around this room,
there are few, are a very much like the first two species
and the old adult with coronary artery disease is
like the last two there, which means that one
of our defense mechanisms that we have is as a young adult,
I hope I'm not insulting everybody or anybody
but you're very pig-like and take that in the appropriate way
but as an older adult you develop coronary artery disease.
And paradoxically, that is the stimulus for growth factors
to be released for the development
of collateral vessels to your advantage
so you become a bit like me.
Yeah, and if-- well, whether I've got coronary artery disease
or not, I'm not sure yet.
I'm sure all of us at a certain age will have a certain level
of blockage.
And there is-- therefore the room has to be divided
into some pigs and some dogs, I'm sorry,
I will fit into the right hand inside.
Now, that doesn't mean you have to be like this guy.
He has got it completely wrong, okay.
He should be on the treadmill even though this chap,
he'll have the collaterals.
He should be on the treadmill.
He's certainly got coronary artery disease,
that's almost guaranteed.
Right, I've mention collateral flow,
I've mentioned the various ways to protect the heart
when you have a heart attack, how to return the blood flow
as quickly as possible.
I want to now come to something called preconditioning
which is very close to my heart which I've spent a number
of years investigating and this particular phenomenon
and how we can best utilize that to the benefit of patients.
Well, what is preconditioning?
Well, this is gonna be quite something
to get your head around, but stopping
and returning blood flow in the coronary arteries
for a few minutes at a time,
paradoxically can protect the heart
from a lethal heart attack.
What it's really saying is that mini heart attacks,
well I mean mini, mini heart-- they're not meant to kill you
but blocking flow, having hypoxia, reducing blood flow
for a few minutes at a time before a lethal heart attack can
significantly protect the heart.
Let me try and convince you with the following slide.
This is muscle taken from the heart which have been sliced
from apex through the base.
It's been subjected to 30 minutes of lethal blood flow,
stoppage of blood flow, lethal ischemia it's called.
And you can see when we stain it,
everything in white here is infarcted muscle, is dead tissue
which will never survive, okay.
So, you really damaged this heart.
Now, if you give this heart before you give it the 30
minutes of lethal insult, if you give it a treatment
and that treatment just consists of stopping blood flow
for 5 minutes, returning blood flow
for 5 minutes before the lethal attack,
look at the difference that you get.
Isn't it absolutely remarkable, the amount of infarction,
the amount of dead tissue is significantly smaller.
And we go into this number of years ago basically because it's
so exciting to find the mechanism of what is happening
in the 5 minutes of ischemia, 5 minutes stopping flow
to give you this most profound protection really set a number
of us to investigate the mechanisms associated in this
because if we can find the mechanism,
then you can develop the right drugs or the right procedures
to institute this in patients.
Well, why does this happen?
And can we exploit it to advantage?
Those are the big questions.
Well, why does it happen?
We think, well, we're almost 100 percent certain
that that phenomenon
of preconditioning activates survival proteins in the heart
which when you then have your lethal insult, they sit in there
and they're ready to protect and prevent the muscle from dying.
Can we exploit it?
That was the other question.
Can we exploit this to our advantage?
Well, we need a model and what I mean by that is not that model,
we need the actual biological laboratory model.
We need something that we can work on in the lab
to prove the hypothesis.
This is one of the models we use.
This is called an isolated diffused heart preparation.
In this case, this is a rat's heart.
The rat has been anesthetized, just has been opened,
the heart has been removed and it's retrogradely perfuse
down the coronary arteries here
with a liquid that simulates blood.
Okay, it's a called a buffer.
It's the Krebs buffer which simulates blood
and that goes on beating for hours.
So what we can do is we can put a suture
around one of the arteries.
>> We can ligate it and give it a heart attack.
And here you can see when we put a blue dye in that heart.
Because we've cut our flow here, everything distal
to that does not have flow and that will have--
you know an area where your heart attack occurs
and your muscle starts to die.
And what we can do is very simply look at the white tissue
which is the dead tissue,
look at the area here that's the light red which is the area
that we're trying to salvage.
You can't cure dead tissue.
Once it's dead it's dead, but there's a lot
of muscle you can save because all that will happen here is
if you don't do something, this white area will extend
through to that light red area.
This is just a graph to show you how protective this
phenomenon is.
If we don't do anything, we'll get about close
to 70 percent infarction.
If we precondition, we can reduce it significantly.
It's extremely a powerful tool.
.Okay, does it occur in man?
Because no matter what I show you in terms of dogs, pigs,
and rabbits, in any species, the most important species is us.
Okay, we have to show whether we can protect in man.
Well, the way we do this is before we get directly into man,
we use human muscle to inves--
excuse me, to investigate this phenomenon.
This is what's happening during bypass surgery
as I showed you earlier.
You can't see this very well but what happens, these pipes
and tubes have to be connected,
this area here in the right atrium.
So the surgeon has to cut off that right atrium.
It's part of the operation.
He throws it away.
One of my clinical research fellows stands here
with a [inaudible], catches it, rushes it back to the laboratory
and there it is and I hope you could see that these are strips
of right atrial muscle.
So we can remove that muscle,
put it into this complicated looking system
and I only show you this to try and pretend
that we're all that clever.
It's not that-- it's quite straightforward.
It's just putting-- I'll show you this picture here.
Looking closer you can see that's a piece
of human muscle 30 minutes
after the patient has-- having the operation.
While the patient is having the operation, we've taken the piece
of muscle back to the laboratory.
And we put it in an organ bath and we can stimulate it
and it could carry on contracting.
Now the wonderful thing
about this is it's not animal, it's human.
So therefore we can do everything that we've done
in the animal setting through to the human
to see whether the same principles apply.
Take that piece of human muscle.
We subjected to a mini heart attack by blocking flow.
And if we don't do anything you can see we get--
we're looking at the amount of muscle that recovers function.
And you can see that if we don't do anything,
we get about 20 percent recovery of function of that muscle.
If we precondition it with a small burst of the ischemia
or burst of hypoxia, before the lethal insult we get
significant protection.
So again, this is [inaudible] concept that we've gone
from the animal setting to man and to human muscle
and we can see protection.
I have put up that picture, to have a drink of water and also
to tell you why am I showing you a Japanese garden?
Well, every thing's got a reason and I happened to be in Japan
at a meeting a number of years ago and we walked
around this particular garden, beautiful, beautiful garden
with a colleague of mine, Mr. Will Pugsley [phonetic]
and he's the cardiothoracic--
he was the cardiothoracic surgeon in our hospital here.
And I remember walking around I said, "Will, time has come
to go from animal to man.
We've got to see if we can do this in patients.
Not in human muscle, even, but in patients because it's
of no use to anybody unless we can exploit this
to the benefit of a patient."
So we went to our ethics committee and that's Will there.
And just to show you a picture what's happened in surgery,
there are lots of people.
There's the fusion, there's hangers on all over the place.
We went to our ethics committee and they gave us approval
to do the following study.
The study comprises of that--
I'll show you this picture of the heart
and I'll show this picture of a clock for a reason.
That's the heart, that's the aorta,
this big mass of artery coming off.
We had permission to clamp that aorta.
Okay, I can see some people going like that.
I was going like that as well.
Let me show you.
In the control hearts where we had--
where the surgeon sewed on three graphs a total of 30 minutes
of injury while he's doing all that work.
In the con-- that was the control.
We in the test group or the preconditioned group,
we blocked the aorta for 3 minutes, we let blood flow back
for 2 minutes, we did it again for 3 minutes
and we let blood flow back for 2 minutes.
Now I promise you, I was in the-- I was at--
I went to see the first operation done
because it was my idea.
And I sat in the corner in an operating theater,
there are lots of people, there's God which is the surgeon
and there's all the lesser.
And I was the least of the lot in the corner
by the door and ready to escape.
Because when you cross exam that aorta for 3 minutes and you look
at the clock, this was the clock in the operating theater,
it's a long time for those 3 minutes to go
and everybody is standing like this doing nothing.
And I was very confident based at all the previous work
that we've done in animals and human muscle
that we would see something beneficial
to that-- for that patient.
Not having said that, it's a long time to wait,
especially when you do it twice.
These are the results that we got.
I'm trying to get this to move on.
Okay, we measured an enzyme called troponin T
which is an enzyme which tells you
if you're injuring your heart, if you heart is damaged.
Before the bypass, the enzyme is not exist--
nonexistent 'cause the heart is not damaged.
During the surgery itself, you get a significant increase
in this enzyme, imply that there are some periprocedural injury
occurring during the bypass surgery.
When we preconditioned those patients with those 2,
3-minute bursts of ischemia reperfusion,
you can see there was a significantly lower level
of that enzyme.
Implying a proof of concept
that preconditioning was highly protective to that patient.
It was tremendously exciting when we did this.
And although this was done in 1997,
you can say why is this routine?
Why is it used routinely?
Well, simply because it's an evasive technique.
Nobody, no surgeon wants to clamp off the aorta.
This was a proof of concept to show that this phenomenon work.
We had to wait another few years to get an idea of how
to take this further and that was done following--
so the question was, is there a noninvasive way?
Can we do this without actually opening the chest cavity aorta?
So, let me just go back.
Preconditioning as I've tried to explain to you is stopping
and returning blood flow
in the coronary artery themselves, okay?
But if you stop and return blood flow in another part
of the body, okay, distal
from the heart itself, you can also protect.
Let me show you what I mean by that.
We call it remote preconditioning.
So in other words, if you precondition the kidney,
the guts or the liver, you can protect the heart so you can--
but these are still invasive techniques.
You have to open up, find the kidney,
find the gut, find the liver.
What about the arm?
What about it?
If we put a blood pressure cuff on the arm and you squeeze it
to make it stop flow for a little bit,
would that not act the same way as preconditioning?
So again, we went to our ethics committee
to do the following proof of concept study.
We took patients, we called it a brief of concept,
we took patients who were having what was called elective
coronary artery bypass surgery routine.
We put a blood pressure cuff on those patients
on while they were asleep.
So they were anesthetized, they didn't feel anything.
You put a blood pressure cuff on the arm and you inflate it
for 5 minutes and you do that-- we did that 3 times.
Then they were wheeled into the surgery for the surgeon
to get on with his job.
Okay, just by the way, putting a blood pressure cuff
on the arm is uncomfortable.
I've done it myself but it's bearable
for these patients who were asleep.
>> So, if we did that, and we repeated it 3 times compared
to a control group which didn't have a blood pressure cuff put
on their arm.
And we mentioned this enzyme troponin again,
what would we see?
Well, this is the profile of the patient's troponin release
over the course of 72 hours.
You can see it's up and it stays up,
implying that there's some injury.
The way we preconditioned by putting a blood pressure cuff
on the arm for 3 minutes twice significantly reduced it.
So just that noninvasive procedure show
that we could protect, and we published this
in the Lancet a couple of years ago, 3 years ago.
Now unfortunate-- that's why I brought this whole thing round
to something called would you give your right arm
to protect your heart?
Because that's exactly what we're doing.
Based on those [inaudible] studies that I showed you,
we built up a story that shows
that we could potentially put a blood pressure cuff on the arm
and protect the heart.
Everybody is asking, well, how is this working?
We answer this question on a daily basis.
We don't have the answer but we think the answer is as follows
and we, we and believe you and me,
the rest of the world is trying to hunt this mechanism
as we speak because it's so potentially important.
When we put a blood pressure cuff on the arm,
we believe that there's a humeral factor,
that means a small peptide,
a small protein that's being released during the period
that you're stopping flow.
So when you return flow, it races to the heart
and protects the heart from injury.
And we're all looking for that at the moment, but even equally
as exciting is that we are undertaking a large study.
What I showed you was before was a small proof of--
a small study showing that we could protect the heart,
proof of concept.
We've been very fortunate to get some funding
over at 1.7 million pounds from the government as well
as the MRC, the NIHR and the BH--
[inaudible] to do the first randomized control study of this
in the world and we started last week.
We've got 2 patients on board and we need
to get many, many more.
But there are 12 centers all around the UK
that are working with us.
So potentially very exciting
to show whether this noninvasive technique can protect.
So I think my time is up here.
What I want to conclude is the following.
I've tried to show you that various ways
to protect your heart when you have a heart attack.
We have thrombolysis, we have coronary artery bypass surgery,
we have been using angioplasty always to return blood flow
to the damaged muscle as quickly as possible.
I've also mentioned the importance
of your own defense mechanism that you have in terms
of developing these important vessels
when you have coronary artery disease.
And then I'll try to show you what happens in cells
and animals and in human muscle and take that rightly
through to man to protect man
and this is what we're trying to do as we speak.
So let me finally add, this is a--
everything I've discussed with you is done in conjunction
with colleagues both here also in the Heart Institute
at the University College Hospital
at University College London itself, and I mean get it also
to our grant awarding bodies
such as the British Heart Foundation, the MRC,
the Welcome Trust and the NIHR.
In addition to Sir Maurice Hatter [phonetic],
the Hatter Foundation, Sir Maurice is in the audience.
We're indebted to him for his long-term support,
to Mr. and Mrs. McDonald, who are new supporters of ours,
we are also indebted to them, as well as the Rosetrees Trust
who are helping us with some of our clinical studies.
On that note, I'm prepared if I've got time
to take some questions.
Thank you very much.
[ Applause ]
>> This is the worst part
when you see hands just go up like this.
>> Referring to those of us of a certain age,
should we try this at home?
>> I guess they tried once.
[ Inaudible Remark ]
>> No, either-- I mean no.
Either you only-- it's only you, it's useful to you
if you know you're gonna have a heart attack
in the next few minutes or-- so you know, leave it to--
what we're trying to do in all seriousness is
if someone's having a heart attack and gets
into an ambulance, we are in talks with London Ambulance
at the moment to see if we can use the London Ambulance
individuals to inflate a balloon while the patient is being taken
to a hospital to set up a protective pathway.
>> Would you say more about the tentative heart muscle not
to regenerate whereas many other organs and parts
of the body do I think, don't they?
>> Yes, you're right, excuse me.
Unfortunately the heart doesn't regenerate.
According to some-- it's some people that say that it might.
But as far as we know, it doesn't regenerate.
I can't give you an intelligent answer as to why,
why the heart was left to other organs to you know,
and other animal species can regenerate anything,
but we can't.
We don't know what it is.
There's a huge amount of funding being put into that
at the moment in terms of stem cell research to see
if individuals can look at that.
I'm often asked why I don't go
into stem cell research 'cause it's exceptionally exciting.
And my answer is quite simple, stick to what you know,
number 1, if I went into stem cell research,
we'd probably muddy the waters.
There's very good people out there doing very good work
and we should get answers in the not too distant future.
So we'll have to wait and see.
So I'm sorry I can't answer your question
as you might have liked.
We all want to know why the heart won't regenerate.
>> Do you know at least how long the survival proteins
last [inaudible]?
>> Very good question, we think they last between 2 and 3 hours.
>> I see, thank you.
>> Yeah. But you'll be pleased to hear that we were the first
to describe what is called the second window of protection.
And the same proteins come back after 24 to 48 hours.
We're not sure why but it is like the first 3 or 4 hours
and then disappears and then there's a second window
and we're trying to.
So, from a clinical point of view, that's very important.
[ Pause ]
[ Simultaneous Talking ]
>> -- the right arm, sorry.
Is this the right arm is literally the right arm,
not the left arm?
>> No, no, no could, no-- I just--
it sounded nicer to say would you give your right arm
and to say would you give your left arm.
So, no, it could be any arm and in fact,
that's a very important point you make, we are now looking
at the legs as well because if you think about it, excuse me,
I'll walk across here, but the leg is much greater muscle mass.
So you could argue that you get a better ischemic burden,
in other words, you get more, more for your buck so to speak.
But squeezing your leg, and we try to investigate now whether,
you know, one arm and two legs is better than--
any organs making it-- making--
stopping blood flow is a benefit, we think.
>> Okay, thank you very much for your lecture.
I was just wondering you mentioned this humeral factor,
where would it come from in your experiments on just muscle?
>> Yeah, that's the very--
we think it happens when you have hypoxia,
when you stop blood flow.
We think either from the mitochondria or various parts
of the cell release a peptide.
And I just came back from America,
I was on a special group of individuals
from the National Institution of Health looking
and asking these very questions that you've just asked
and the National Institution of Health
in America are putting millions of pounds into this trying
to find out what this factor is.
And we in Europe are also developing experiments to try
and find out what this factor is because of course it was real
and if it's what causes protection, then we could talk
at that perfectly, but we think it's just--
we're not sure what it is, where it's coming from,
but you can take a heart, you can make--
you can take a bit of muscle, you can take some of the blood,
you can put it into another species
and you can give it protection.
So it's transferring some factor in the blood, some small peptide
in the blood that can be protected.
>> I'm afraid that's all we have time for today and sorry
about that and thank you very much for coming and I like you
to join me in thanking Professor [inaudible]
for a every stimulating talk.
Thank you.
[ Applause ]