Evolutionary origins of the right

ventricle

S Magder

Department of Critical Care,

McGill University Health Centre

Fully separated four chamber heart only

evolved in birds and mammals

What are the evolutionary advantages?

Why examine the evolutionary

development of the heart?

• Understanding evolutionary development gives us

a better understanding of why an organ is what it is – its advantages and disadvantages

• It helps us better understand the limits that can

occur with disease

“Diploblastic” Only 2 cell types

Endoderm and Ectoderm

Simple passages allowed:

-Circulation of sea water

-Nutrient absorption

-Reproduction (filter sperm)

All combined!

800 – 700 MYA

-Invagination from gut,

not enclosed, pulsatile,

not unidirectionalSymmetric body plan

Drosophila: - cardio-aorta valve, pericardial cells

-O2 can be transferred directly from

airway to mitochondria

• Separate gut and gas exchange

• Enclosed vessels

• Early myocardial cells

Beginnings of a circulatory system

550 MYA

Vertebrates

550 MYA

340 MYA

320-250 MYA220 MYA

170 MYA

Beginning of

CV system

Fish Heart

• Single atrium and ventricle

• Can create pulsatile flow at different rates and increase CO

Limitations

Heart gets least

saturated blood

Gas exchange area gets

highest BP

Must be a tough structure

But –

• Fish do not have to support weight

• Locomotion is simpler

• Temperature regulated by outside

• Water readily available

• Food abundant

Increase in CO in

Tuna ( a fish athlete!)

is ~14%

But 500 % in young

male

Amphibian

heart

2 Atria

1 Ventricle

Mixing

https://blogs.ubc.ca/mrpletsch/2017/02/18/class-amphibia/

Pulmonary compartment

is now separated from

the systemic circulation

and can be protected

But:

• Systemic O2 Sat is still

diluted

• Heart does not get

fully saturated blood

• With muscle activity,

less blood flowx to

lungs and capilllairies

Reptilian

heart

Third outflow vessel with

sphincter like property can

reduce desaturation of

arterial blood by reducing

flow to lungs when more

oxygenated blood is needed

systemically

BUT:

This means they cannot

work and breath!

Fishman and Chein 1997

“spongy” “Compacted”

Genetic differences of RV & LV

• RV controlled by Hand2 (discovered 1993) whereas LV is controlled

by Hand1

• LV comes from the “anterior” heart field whereas the RV comes from

a second heart field that is likely genetically more primitive

Srivastava Nature 2000;407:221 and Cell 2006;126:1037

RV cells

Advantage to fully developed RV with separate

pulmonary and systemic circulations

• Allows for low pressure pulmonary circuit despite

high systemic pressures

– Therefore more delicate structure

• Fully saturated coronary arteries

• High pressure systemic circulation for better flow

distribution according to need

• Aerobic capacity of mammals is 12 x that of next

species (reptiles)

• Birds can be as much as 20x

If you can get by the first 10 to

30 seconds you will be ok!

VO2 ml/min/kg

Resting: 3.5

Max: 45

VO2 ml/min/kg

Resting: 0.3

Max: 10

BUT:

• Blood flow through the lung is susceptible of

changes in Ppl and Transpulmonary pressure

• RV is not designed to tolerate high pressure

loads

And:

• RV handles flow well and normally does not

limit maximum flow

• (but there is a price to pay when it does not

lower venous pressures)

Can you survive without an RV?

Fontan Physiology

• In-series circulation with a single pumping chamber

http://www.childrenshospital.org/cfapps/mml/index.cfm?CAT=media&MEDIA_ID=1837

Patients without an RV

• “Fontan Repair”

– Used for pt with tricuspid atresia, single venticles (hypoplastic R

or L) and other similar congenital abnormalities

• Vena Cava are attached directly to the pulmonary circuit

• Can have near normal VO2 max

– Eg 24 y/o with peak VO2 of 2.6 L/min (~ 85% predicted)

• BUT: cost is systemic venous congestion (protein loosing

enteropathy and cirrhosis in their 40-50s

• Susceptible to rising PVR and LV diastolic pressure

Why then is there a problem when RV function

is decreased if you can live without an RV?

• During exercise, the contracting muscles act like a venous

pump

• Contractions with a dilated heart can lead to tricuspid

regurgitation

• MAJOR issue is the need to be able to handle an

increased load (PVR, high left sided pressures)

– Limitation of filling becomes the problem

– End up with systemic venous congestion with no increase in Q

– RV - LV interaction (RV preload becomes RV afterload

P

VQ

A. Excess filling of the RV increases the stiffness of the RV free wall

-This means greater transmission of RV diastolic pressure to the left

heart.

B. Rising LV-diastolic pressure decreases pulmonary emptying

C. This raises PAP and RV preload becomes RV afterload

RV preload becomes RV afterload

A

B

Normal Over-filled RV C

Q

Pra

Q

Part

RV preload becomes RV afterload

PAP often does not increase

Increased RV load leads to decreased RV function

(depressed curve from increased afterload)

Increased

outflow

pressure

(↑ LAP)

Lower Q same PAP

Conclusions

• The RV is the original heart; the LV is a late arrival

• You can function without an RV if PVR and LA pressures

are low

• Presence of RV keeps Pra low and avoids upstream

organ congestion

• Cauterized the free wall of the right heart

– No change in CVP

• Functional status maintained

Starr et al 1943 - continued

However:

• animals were anaesthetized and presumably had normal

Pulmonary pressures

• Cardiac output not assessed

• “long term – conscious functional status was only assessed in 3

animals

– 1 died at surgery

– 1 lasted only 72 hr

– the 3rd lasted 3 months and is the basis for the claim

So what does the right heart do?

Need to go back to what makes

the blood go around

Why couldn’t you just have the

gas exchange region in series

with the drainage of the blood

from all regions?

or

What does the right ventricle actually do?

Right heart is an excellent flow generator

• Role of right heart in cardiac function is to lower right atrial

pressure (“permissive”)

• This key function is often not appreciated

– It is easier to assess pressure tolerance

– Pressure generation is key function of left ventricle and attracts

comparisons

– Need for increased flow in the face of increased pressure is a

major problem for the RV but a hard one to assess.

Limits of RV

• No left sided effect without right sided effect

• Heart-Lung interactions

Alv

L R

MSFP

Fishman and Chein 1997

Clinical example mismatch of RV

flow generation and “need” • Post operative cardiac surgery patient

• CI 3.2 L/min/m2

• CVP= 15; Ppao =12 mmHg

• LV looks normal (EF = 70%)

• BUT – systolic arterial pressure = 70 mmHg and

on large doses of pressors

• What’s wrong?

Systemic resistance fell due to sepsis. Flow

needed to be greater than 3.2 to maintain arterial

pressure but that was all this RV could do

No left sided success without

right sided success

Implication of RV limitation

• Ppao should not be used as guide for volume management

for cardiac output

• Echocardiography of LV volume and function are also not

good guides

Overall implications of two sided heart with

gas exchange between the two chambers

• Allows for high aerobic performance

• Did dinosaurs have a 4 chamber heart?

– Likely did so that the large dinosaurs could

have sufficient arterial pressure to perfuse their

heads but still a subject of speculation

Pressure tolerance of the RV

Importance of arterial pressure

Harrison et al. Ex post Fontan repair

Although pt reported status was good

measured values were not

Control Fontan

(mean ± SD)

Max work load 1,004±190 548±171

(kpm)

Max VO2 42.4±10.0 14.8±4.5

(ml/kg/min)

Evolutionary Values of RV - 1

• With a single ventricle there is mixing

of fully saturated and unsaturated

blood

– Therefore blood perfusing all regions of

the body is not fully saturated

– This is solved by having the gas-

exchange region between two pumping

chambers

Evolutionary Values of RV - 2

• With two ventricles it is possible to have a

low pressure in the gas exchange region and

a high pressure in the systemic arterial

system

– Low pulmonary pressure allowed development

of delicate lungs which can handle larger

volumes of gas and efficiently exchange gases

– High systemic pressures allow regional

decreases in resistance to distribute blood flow

according to tissue needs

Evolutionary Values of RV - 3

• The high systemic pressure with a two

chamber heart allows for a coronary

circulation that has fully saturated blood

and a high perfusion pressure

– This allows high aerobic performance by the

heart and thus high cardiac outputs

Genetic differences of RV & LV

• RV controlled by Hand2 (discovered 1993) whereas LV is controlled

by Hand1

• LV comes from the “anterior” heart field whereas the RV comes from

a second heart field that is likely genetically more primitive

Srivastava Nature 2000;407:221 and Cell 2006;126:1037

RV cells

RV and LV have different properties

• Pharmacological

• Electrical responses

• Force generation

α1-adrenergic receptors stimulation has contrasting inotropic

effects on left versus right ventricular myocardium. Wang et

al Am J Physiology 2006; 291:H2013

PE

PE

Electrophysiological differences of RV and LVKondo et al J. Physiol 2006; 571.1:131

Increased

shortening

Little change in

shorting length with

decreased frequency

Peak RV sarcomere

shortining less than LV

Endo

120

mmHg

A B

20 120

RV and LV have different embryological

origins

Fully separated four chamber heart only

evolved in birds and mammals

Overall implications of two sided heart with

gas exchange between the two chambers

• Allows for high aerobic performance

• Did dinosaurs have a 4 chamber heart?

– Likely did so that the large dinosaurs could

have sufficient arterial pressure to perfuse their

heads but still a subject of speculation