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
800 700 MYA Diploblastic Only 2 cell types Endoderm and Ectoderm Simple passages allowed: -Circulation of sea water -Nutrient absorption -Reproduction (filter sperm) All combined!
Symmetric body plan -Invagination from gut, not enclosed, pulsatile, not unidirectional Drosophila: - cardio-aorta valve, pericardial cells -O 2 can be transferred directly from airway to mitochondria
550 MYA Separate gut and gas exchange Enclosed vessels Early myocardial cells Beginnings of a circulatory system Vertebrates
550 MYA Beginning of CV system 340 MYA 320-250 MYA 220 MYA 170 MYA
Fish Heart Single atrium and ventricle Can create pulsatile flow at different rates and increase CO
Limitations 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 Heart gets least saturated blood Gas exchange area gets highest BP Must be a tough structure
2 Atria Amphibian heart Mixing 1 Ventricle
Pulmonary compartment is now separated from the systemic circulation and can be protected But: Systemic O 2 Sat is still diluted Heart does not get fully saturated blood With muscle activity, less blood flowx to lungs and capilllairies https://blogs.ubc.ca/mrpletsch/2017/02/18/class-amphibia/
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!
spongy Compacted Fishman and Chein 1997
Genetic differences of RV & LV RV cells 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
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! VO 2 ml/min/kg Resting: 0.3 Max: 10 VO 2 ml/min/kg Resting: 3.5 Max: 45
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?c AT=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 VO 2 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
RV preload becomes RV afterload Normal Over-filled RV C P B A Q V 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 PAP often does not increase Q Q Lower Q same PAP Increased outflow pressure ( LAP) Pra Increased RV load leads to decreased RV function (depressed curve from increased afterload) Part
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 3 rd 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
Alv MSFP L R No left sided effect without right sided effect Heart-Lung interactions
Fishman and Chein 1997
Clinical example mismatch of RV flow generation and need Post operative cardiac surgery patient CI 3.2 L/min/m 2 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 (mean ± SD) Fontan Max work load 1,004±190 548±171 (kpm) Max VO 2 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 gasexchange 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 cells 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 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 LV Kondo et al J. Physiol 2006; 571.1:131 Little change in shorting length with decreased frequency Peak RV sarcomere shortining less than LV Endo Increased shortening
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