HBF-ii_2024-L9_slides-chung.pdf

Cardiac Function (Integrated) HBFII Lecture 9 Wayne State University - School of Medicine 2024 Charles S Chung PhD Associate Professor Department of Physiology [email protected] Role of the Heart: Cardiac Outpu...

Cardiac Function (Integrated) HBFII Lecture 9 Wayne State University - School of Medicine 2024 Charles S Chung PhD Associate Professor Department of Physiology [email protected] Role of the Heart: Cardiac Output A heart must move blood through the body Blood is a fluid We’ve learned about the cell physiology How does this translate to the whole heart and relate to cardiac output? What other indexes might we observe? Learning Objectives Define Laplace’s Law Understand how changing Recreate the Wiggers’ afterload normally alters the Diagram and define its Pressure-Volume loop and its phases by ventricular valve relationship to contractility opening and closure Describe the Frank-Starling Describe the major heart relationship, how the sounds and their genesis relationship requires a change in preload, and its link Recreate the relationship to length-dependent between the Wiggers’ activation Diagram and a Pressure- Volume Loop Determine cardiac output Cell Physiology Suggested Review Concepts Cardiac Anatomy Ventricular chambers Atrial Chambers Major Veins and Arteries All 4 Valves Krebs Cycle LaPlace’s Law LaPlace’s Law Need to generate Pressure Bernoulli’s principle- Fluid moves with a pressure gradient from higher pressure to lower pressure Contraction can generate pressure Valves prevent flow in the “wrong” direction Valves open with a pressure gradient http://www.old-ib.bioninja.com.au/standard-level/topic-6-human-health-and/62-the-transport-system.html LaPlace’s Law Cardiac shape relates to pressure Heart is not a sphere, but can use this as an approximation r u Pressure (P) 2 𝜎𝜎 𝑢𝑢 𝑃𝑃 = 𝑟𝑟 Wall stress (force, tension, σ) in the wall Radius (r) of the sphere Thickness (u) of the wall Thickness is sometimes ignored LaPlace’s Law Clinical Echocardiography: determine r, u Multiple views for diameter Short axis B-Mode PLAX B-Mode M-Mode (Mid Myocardial,PLAX) r u u 2r https://www.asecho.org/guidelines-search/ LaPlace’s Law Cardiac shape relates to pressure Heart is not a sphere, but can Larger radius=less pressure use this as an approximation can be generated Dilated cardiomyopathies Pressure (P) 2 𝜎𝜎 𝑢𝑢 Self Test: Why might a wall 𝑃𝑃 = thicken or LV chamber get smaller 𝑟𝑟 in hypertension? Wall stress (force, tension, σ) in the wall Note: If it hasn’t already, Laplace’s law will come up again Radius (r) of the sphere in physiology Thickness (u) of the wall Cylinders won’t have the “2” Thickness is sometimes ignored Often won’t see thickness (u), for example: alveoli Wiggers’ Diagram Phases of the Cardiac Cycle Want a sequence linking the contraction with pressure and volume (or flow, the change in volume) Focus on Left Ventricle Wiggers’ Diagram Phases of the Cardiac Cycle Action potentials cause contraction ECG shows how action potentials move along the heart Contraction moves blood by increasing pressure Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle P-wave is atrial depolarization and contraction So this is a phase of atrial contraction and filling of the ventricle Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle QRS complex is ventricular depolarization and contraction Ventricular pressure goes up, closing the mitral valve All valves are closed, so phase is isovolumic (same- volume) i.e. Isovolumic Contraction Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle When the LV pressure exceeds the pressure in the aorta (dashed line), the aortic valve opens Blood exits from the heart, reducing its volume i.e. Ejection Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle As the heart’s contraction fades and the heart begins to relax, the aortic valve closes The heart relaxes and pressure falls (wall tension drops) despite there being no open valves i.e. isovolumic relaxation Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle The heart’s relaxation makes the LV pressure drop below the atrial pressure so the mitral valve opens This begins filling of the heart This filling is typically rapid i.e. Early Rapid Filling Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle If the heart rate is slow enough, there is a separation of the early rapid filling and the next p-wave There is little flow during this period, it is a “rest” phase i.e. Diastasis Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle A new P-wave occurs, causing more atrial filling. This phase is considered “late” because it comes after the prior filling i.e. Late Atrial Filling or Atrial Systole Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle Contraction and ejection = Systole Ventricular Relaxation and Filling = Diastole Note: Systole roughly correlates with QT interval But systole and diastole are defined by valve closing, NOT by ecg, etc Guyton 9-8 Wiggers’ Diagram Phases of the Cardiac Cycle Contraction and ejection = Systole Ventricular Relaxation and Filling = Diastole Note: Systole roughly correlates with QT interval But systole and diastole are defined by valve closing, NOT by ECG, etc Guyton 9-8 Wiggers’ Diagram Clinical Echocardiography: timing of valves M-Mode (Mitral valve, PLAX) E A https://www.asecho.org/guidelines-search/ Wiggers’ Diagram Phases of the Cardiac Cycle Volume and Flow Early Rapid Filling “E-Wave” Late Atrial Filling “A-wave” A-wave is during ATRIAL systole A-wave is during VENTRICULAR diastole Ao of Volume Derivative Ejection =Flow E-wave A-wave Guyton 9-8 Wiggers’ Diagram Clinical Echocardiography: flow for durations Pulsed Wave Doppler (transmitral flow, Apical 4-ch) E A Diastasis IVRT https://www.asecho.org/guidelines-search/ Wiggers’ Diagram Clinical Echocardiography: flow for durations E- and A-waves don’t change Exercise: Why might the E- much with heart rate wave or ejection duration change if a P-wave fires Diastasis is shortened (lost) earlier? What is constant? Chung Karamanoglu Kovacs Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2003-8. Wiggers’ Diagram Phases of the Cardiac Cycle Integration: Why is decremental conduction of the AV node helpful? (What would happen to atrial systole if there was no decremental conduction?) Guyton 9-8 Wiggers’ Diagram LV vs RV Notes about right ventricle RV and LV contract at similar (RV) versus left ventricle (LV) times, but filling or ejection in the RV can be noticeably RV wall is thinner (smaller u) different than the LV RV does not generate as much Typically pathophysiologic when pressure they are dyssynchronous peak RV pressure ~25 mmHg Peak LV pressure ~120 mmHg Guyton 9-8 Heart Sounds Heart Sounds Auscultation Sources of Sounds: Listening to sounds Valves Common: heart, lung, pulse When valves shut, they vibrate pressure (Korotkoff sound) Might not be a significant Auscultation of the heart listens contributor to sounds of the heart Deceleration of blood Provides information on Slowing of blood causes a sound changing blood flow wave Heart Sounds Four heart sounds 1st as the mitral valve closes (S1) “Lub” 2nd as the aortic valve closes opens (S2) “Dub” 3rd as blood decelerates during early rapid filling (S3) 4th as blood decelerates during late atrial filling (S4) 3rd and 4th are typically pathologic (stiff or dilated 4th ventricles) Guyton 9-8 Lub Dub Lub Dub Heart Sounds LV and RV be relatively General Heart Sound synchronized examples: If the RV does not close the https://www.merckmanuals.com /professional/cardiovascular- pulmonary valve at the same disorders/approach-to-the- time the LV closes the aortic cardiac-patient/cardiac- valve, it may “Split” auscultation S2 becomes A2, P2, for an https://stanfordmedicine25.stan aortic and pulmonary sound ford.edu/the25/cardiac.html Wiggers’ Diagram Integration ECG indicates cellular electrophysiology Pressure (and change in volume) is generated by contraction (excitation- contraction coupling, Myosin ATPase) Pressure can be modulated by shape of heart (LaPlace’s Law) Guyton 9-8 Wiggers’ Diagram Summary Blood flow and valve opening are Wiggers’ Phases as defined by the pressure gradient dependent Left Ventricle: Systole Isovolumic Contraction LaPlace’s Law connects myocyte Ejection contraction to ventricular pressure Diastole Isovolumic Relaxation Wiggers’ diagram defines cardiac Early Rapid Filling phases by valve opening/closure Diastasis (if HR is slow enough) Late Atrial Filling (Atrial Systole) Heart sounds are from valve and flow changes Pressure-Volume Relationships Pressure-Volume Relationships 120 100 80 Pressure 60 40 20 MVC 0 30 90 130 Volume Guyton 9-8 Pressure-Volume Relationships Isovolumic Contraction 120 100 80 AoVO Pressure 60 IVC 40 20 MVC 0 30 90 130 Volume Guyton 9-8 Pressure-Volume Relationships Ejection 120 Ejection 100 AoVC 80 AoVO Pressure 60 IVC 40 20 MVC 0 30 90 130 Volume Guyton 9-8 Pressure-Volume Relationships Isovolumic Relaxation 120 Ejection 100 AoVC 80 AoVO Pressure 60 IVR IVC 40 20 MVO MVC 0 30 90 130 Volume Guyton 9-8 Pressure-Volume Relationships Early Rapid Filling 120 Ejection 100 AoVC 80 AoVO Pressure 60 IVR IVC 40 20 MVO E MVC 0 30 90 130 Volume Guyton 9-8 Pressure-Volume Relationships Diastasis 120 Ejection 100 AoVC 80 AoVO Pressure 60 IVR IVC 40 20 MVO E MVC 0 30 90 130 Volume Diastasis Guyton 9-8 Pressure-Volume Relationships Late Atrial Filling 120 Ejection 100 AoVC 80 AoVO Pressure 60 IVR IVC 40 20 MVO A E MVC 0 30 90 130 Volume Diastasis Guyton 9-8 Pressure-Volume Relationships Cardiac Function End diastolic volume (EDV)- 120 Ejection volume of the blood when the 100 mitral valve closes AoVC End systolic volume (ESV)- 80 AoVO volume of blood in the heart Pressure 60 when the aortic valve closes IVR IVC Stroke volume (SV)- difference between EDV and ESV 40 20 A Ejection fraction (EF)- percent of blood ejected (>50% normal) MVO E MVC 0 30 90 130 100*SV/EDV Volume 100*(EDV-ESV)/EDV ESV SV EDV LaPlace’s Law Clinical Echocardiography: determine r Use r and length at end systole and diastole to get EDV, ESV Short axis B-Mode PLAX B-Mode M-Mode (Mid Myocardial,PLAX) r u u 2r https://www.asecho.org/guidelines-search/ Pressure-Volume Relationships Cardiac Function 120 Ejection 100 AoVC 80 AoVO Pressure 60 IVR IVC 40 20 MVO A E MVC 0 30 90 130 Volume Diastasis Guyton 9-8 Pressure-Volume Relationships Afterload: Defining Contractility/Inotropy Pressure-Volume Relationships Afterload: Defining Contractility/Inotropy AoVO Changing Afterload 120 Changing the conditions the 100 AoVO ventricle faces during AoVC contraction 80 AoVO i.e. changing aortic pressure Pressure AoVO 60 AoVO Changes aortic valve opening 40 (AoVO) and closing (AoVC) Changes ESV 20 MVC Does not change mitral valve 0 closing (MVC) 30 90 130 Volume Self Test: Did we change preload? Pressure-Volume Relationships Afterload: Defining Contractility/Inotropy AoVO Connect the end systolic 120 points 100 AoVC Y-value: AoVC 80 X-value: ESV Pressure AoVO 60 Slope of the line defines 40 Contractility/Inotropy 20 MVC 0 30 90 130 Volume Pressure-Volume Relationships Reducing Contractility/Inotropy Decrease in inotropy 120 (orange→green) 100 AoVC Decreases stroke volume 80 Does not change AoVC, etc Pressure Could change ESV/MVC 60 40 Mechanisms 20 Reduce calcium release MVC 0 Reduce thin filament activation 30 90 Volume 130 Inhibit myosin ATPase Pressure-Volume Relationships Preload Pressure-Volume Relationships Preload Changing preload 120 Changing how much blood is in the heart before contraction 100 AoVC Changes mitral valve closing 80 AoVO Pressure (MVC), changing the ESV 60 The change in MVC is defined by the Passive Forces (titin, 40 collagen) 20 MVC 0 MVC 30 90 130 Volume Pressure-Volume Relationships Preload Changing preload Does not change aortic valve 120 opening or closing 100 AoVC Self Test: Did we change afterload? 80 AoVO Pressure Does not change ESV Self Test: Can we measure 60 Inotropy? 40 Changes Stroke Volume i.e. Frank-Starling Law 20 MVC At longer length/higher volume, myocytes/heart contracts more 0 MVC vigorously 30 90 130 Volume Pressure-Volume Relationships Frank-Starling Mechanism Pressure-Volume Relationships Frank-Starling Mechanism Heart Failure/ CVD 120 100 80 Pressure 60 Low Calcium High Calcium Low Calcium High Calcium Heart Failure/ CVD 40 20 0 30 90 130 Volume Sequeira et al Circulation Research. 2013;112:1491–1505 Low Calcium High Calcium Low Calcium High Calcium Pressure-Volume Relationships Frank-Starling Mechanism Heart Failure/ CVD 120 100 80 Pressure 60 Low Calcium High Calcium Low Calcium High Calcium Heart Failure/ CVD 40 20 0 30 90 130 Volume Sequeira et al Circulation Research. 2013;112:1491–1505 Low Calcium High Calcium Low Calcium High Calcium Pressure-Volume Relationships Frank-Starling Mechanism 120 120 100 100 80 80 Pressure Pressure 60 60 40 40 20 20 Normal Heart: Dysfunctional Heart: 0 0 30 90 130 30 90 130 Volume Volume Myocardium generates more Myocardium generates same tension than expected at longer force at all lengths length Inhibits ability to contract Contributes to greater stroke Reduces EF volume Pressure-Volume Relationships Frank-Starling Law A larger preload will generate a larger stroke volume Increased inotropy produces Increased inotropy Stroke Volume a greater increase in stroke volume Note: Preload may be defined as: EDV End Diastolic Pressure Right Atrial Pressure Preload Pressure-Volume Relationships Frank-Starling vs Length Dependent Activation Pressure-Volume Relationships Frank-Starling vs Length Dependent Activation 120 120 100 100 80 80 Pressure Pressure 60 60 40 40 20 20 0 0 30 90 130 30 90 130 Volume Volume Pressure-Volume Relationships Frank-Starling vs Length Dependent Activation Tension (% of maximal) End Systolic Pressure- 120 Total Force Volume Relationship (Inotropy, Contractility) 100 100 Calcium Release Excitation- Thin Filament Activation 80 Contraction 80 Myosin ATPase Coupling Pressure 60 60 Actual tension End Diastolic Pressure- 40 Volume Relationship 40 (Passive Stiffness) Titin 20 Titin Collagen Extracellular matrix 20 Tension Expected 0 from LDA 30 90 130 0 Volume % Length 80 100 120 1.6 2.0 2.4 Approx cardiac Sarcomere Length [um] Pressure-Volume Relationships Oxygen Consumption and Work Pressure-Volume Relationships Oxygen Consumption and Work The heart uses a lot of ATP Cardiac State MVO2 (ml O2/min per 100g) Myosin Arrested heart 2 SERCA Resting heart rate 8 Na+-K+-ATPase Heavy exercise 70 … O2 Consumption ATP generated in Organ (ml O2/min per 100g) mitochondria (uses oxygen) Brain 3 Kidney 5 Heart uses a lot of oxygen Skin 0.2 Resting muscle 1 Contracting muscle 50 Tuomainen and Tavi. Exp Cell Res. 2017 Nov 1;360(1):12-18. Pressure-Volume Relationships Oxygen Consumption and Work MVO2 Cardiac State (ml O2/min per 100g) Arrested heart 2 Resting heart rate 8 Heavy exercise 70 O2 Consumption Organ (ml O2/min per 100g) Brain 3 Kidney 5 Skin 0.2 Resting muscle 1 Contracting muscle 50 Tuomainen and Tavi. Exp Cell Res. 2017 Nov 1;360(1):12-18. Pressure-Volume Relationships Oxygen Consumption and Work ATP is converted to Work Work (effort) is done to move 120 MAP 100 AoVC the blood 80 Work=area of PV loop Pressure AREA= 60 Work done to For the course, one can move blood out of LV assume that it’s a rectangle 40 The top is the mean arterial 20 pressure (MAP) MVC The bottom is diastolic pressure 0 30 90 130 Work=stroke volume x (MAP- Volume diastolic pressure) ESV SV EDV Pressure-Volume Relationships Oxygen Consumption and Work Self Test: Cardioplegia solution is typically a high potassium concentration solution used for stopping cardiac contraction Why is cardioplegia important during transplant? Hint: Given the energy requirements for the myosin ATPase, SERCA, why is it good to not depolarize the heart? Cardiac Output Cardiac Output Fick’s Principle Gold Standard method Measure O2/CO2 Measure arterial and venous oxygen content More in Pulmonary/Respiratory Module CO = O2 uptake (ml O2/min.) / A-V O2 diff. (ml O2/L blood) = rate of O2 consumption / (arterial O2 content - venous O2 content) = Units of L/min Cardiac Output Cardiac Function Method Heart ejects liters of blood 120 equivalent to the Stroke 100 AoVC Volume (SV) 80 Heart ejects them for each Pressure 60 beat over time 40 Cardiac output: 20 CO = SV * HR MC In addition to same units, 0 30 90 130 correlated experimentally Volume ESV SV EDV Cardiac Output Clinical Echocardiography: determine volume Volumes from B-Mode Integrate aortic flow (times valve area) Pulsed Wave Doppler (Aortic Arch) Diastole RR Apical 4 or 2 Chamber Systole Ao outflow https://www.asecho.org/guidelines-search/ Cardiac Output Self Test: How can you adjust CO? Lung parameters? Heart parameters? If a person bleeds out, what will happen to preload? Afterload? Cardiac Function Diastolic Function Discussion was primarily Diastolic function has two regarding systole components Contractility/inotropy Relaxation Ejection of blood Related to Isovolumic Relaxation and early filling Stiffness Related to EDPVR Clinically, diastolic dysfunction is now more common than systolic dysfunction PV Loops and Cardiac Output Summary Pressure-volume relationships provide information similar to myocyte Obtain contractility/inotropy by changing afterload Frank-Starling: higher preload, more powerful ejection (greater stroke volume) Related to Length Dependent Activation Myosin ATPase is major consumer of oxygen in the heart Cardiac output Fick’s method CO=SV*HR Final Integration Putting together 4 Lectures: L6. Myocyte action potential and L8. Increased cytosolic calcium excitation driven by sodium allows troponin/tropomyosin to (myocytes), potassium,… move and allow myosin binding L6. Myocyte excitation moves from L8. Myosin ATPase generates force cell to cell via gap junctions L9. Cardiac structure transmits force L7. The electrocardiogram can track (tension/stress) into pressure the path of depolarization L9. Inotropy, work, and cardiac L8. Calcium-induced calcium release output generated and impacted by RyR causes increases in by all of the above cytosolic calcium