Evolutionary origins of the right ventricle. S Magder Department of Critical Care, McGill University Health Centre

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1 Evolutionary origins of the right ventricle S Magder Department of Critical Care, McGill University Health Centre

2 Fully separated four chamber heart only evolved in birds and mammals What are the evolutionary advantages?

3 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

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6 MYA Diploblastic Only 2 cell types Endoderm and Ectoderm Simple passages allowed: -Circulation of sea water -Nutrient absorption -Reproduction (filter sperm) All combined!

7 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

8 550 MYA Separate gut and gas exchange Enclosed vessels Early myocardial cells Beginnings of a circulatory system Vertebrates

9 550 MYA Beginning of CV system 340 MYA MYA 220 MYA 170 MYA

10 Fish Heart Single atrium and ventricle Can create pulsatile flow at different rates and increase CO

11 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

12 2 Atria Amphibian heart Mixing 1 Ventricle

13 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

14 Reptilian heart

15 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!

16 spongy Compacted Fishman and Chein 1997

17 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

18 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

19 Aerobic capacity of mammals is 12 x that of next species (reptiles) Birds can be as much as 20x

20 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

21 BUT: Blood flow through the lung is susceptible of changes in Ppl and Transpulmonary pressure RV is not designed to tolerate high pressure loads

22 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)

23 Can you survive without an RV?

24 Fontan Physiology In-series circulation with a single pumping chamber AT=media&MEDIA_ID=1837

25 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

26 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

27 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

28 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

29 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

30 Cauterized the free wall of the right heart No change in CVP Functional status maintained

31 Starr et al 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

32 So what does the right heart do? Need to go back to what makes the blood go around

33 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?

34 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.

35 Limits of RV

36 Alv MSFP L R No left sided effect without right sided effect Heart-Lung interactions

37 Fishman and Chein 1997

38 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

39 No left sided success without right sided success

40 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

41 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

42 Pressure tolerance of the RV Importance of arterial pressure

43 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± ±171 (kpm) Max VO ± ±4.5 (ml/kg/min)

44 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

45 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

46 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

47 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

48 RV and LV have different properties Pharmacological Electrical responses Force generation

49 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

50 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

51 120 mmhg A B

52 RV and LV have different embryological origins

53 Fully separated four chamber heart only evolved in birds and mammals

54 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