Evolutionary origins of the right - PDF Document

Presentation Transcript

  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

  4. 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!

  5. -Invagination from gut, not enclosed, pulsatile, not unidirectional Symmetric body plan Drosophila: - cardio-aorta valve, pericardial cells -O2can be transferred directly from airway to mitochondria

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

  7. Beginning of CV system 550 MYA 340 MYA 170 MYA 320-250 MYA 220 MYA

  8. Fish Heart • Single atrium and ventricle • Can create pulsatile flow at different rates and increase CO

  9. 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 Gas exchange area gets highest BP Must be a tough structure Heart gets least saturated blood

  10. 2 Atria Amphibian heart Mixing 1 Ventricle

  11. Pulmonary compartment is now separated from the systemic circulation and can be protected But: • Systemic O2Sat 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/

  12. Reptilian heart

  13. 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!

  14. “spongy” “Compacted” Fishman and Chein 1997

  15. 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

  16. 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

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

  18. If you can get by the first 10 to 30 seconds you will be ok! VO2ml/min/kg Resting: 3.5 Max: 45 VO2ml/min/kg Resting: 0.3 Max: 10

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

  20. 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)

  21. Can you survive without an RV?

  22. Fontan Physiology • In-series circulation with a single pumping chamber http://www.childrenshospital.org/cfapps/mml/index.cfm?C AT=media&MEDIA_ID=1837

  23. 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 VO2of 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

  24. 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

  25. 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

  26. RV preload becomes RV afterload PAP often does not increase Lower Q same PAP Q Q Increased outflow pressure (↑ LAP) Part Pra Increased RV load leads to decreased RV function (depressed curve from increased afterload)

  27. 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

  28. • Cauterized the free wall of the right heart – No change in CVP • Functional status maintained

  29. 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 3rdlasted 3 months and is the basis for the claim

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

  31. 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?

  32. 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.

  33. Limits of RV

  34. MSFP Alv R L • No left sided effect without right sided effect • Heart-Lung interactions

  35. Fishman and Chein 1997

  36. 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

  37. No left sided success without right sided success

  38. 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

  39. 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

  40. Pressure tolerance of the RV Importance of arterial pressure

  41. Harrison et al. Ex post Fontan repair Although pt reported status was good measured values were not Control (mean ± SD) 1,004±190 Fontan Max work load (kpm) Max VO2 (ml/kg/min) 548±171 42.4±10.0 14.8±4.5

  42. 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

  43. 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

  44. 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

  45. 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

  46. RV and LV have different properties • Pharmacological • Electrical responses • Force generation

  47. 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

  48. 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