MEDI323 Heart as a Pump Dr. Greg Peoples 2024 PDF

Week 6 and 7: Heart as a pump: Part I and II Dr. Greg Peoples ([email protected]) MEDI 323: Cardiorespiratroy studies  Objectives of the lecture By the end of this lecture you will have completed: Describe the P-V relationship of the cardiac cycle Explain how preload and...

Week 6 and 7: Heart as a pump: Part I and II Dr. Greg Peoples ([email protected]) MEDI 323: Cardiorespiratroy studies  Objectives of the lecture By the end of this lecture you will have completed: Describe the P-V relationship of the cardiac cycle Explain how preload and afterload modify CO. Give examples of pathology that alters the P-V relationship Define heart failure Explain the mechanism(s) of HF.  The heart as a pump Aorta Left atrium Aortic Mitral Valve Valve Left Ventricle Ejection Diastolic End Isovolumic (systole) Filling Diastole Contraction (systole) End Systolic Volume  Pressure & volume measurements Femoral, brachial, jugular vein catheter – right atrium, ventricle, pulmonary artery pressure Femoral, brachial artery catheter – aorta, left ventricle pressure Guided by x-ray, balloon catheter. Pulmonary wedge pressure RA RV PA Lungs LA LV Aorta 15-30 15-30 100-140 100-140 0-8 1 - 10 1 - 10 1-10 0-8 4-12 3-12 60-90  Femoral artery most common site due to size and location (superficial and close to inguinal ligament) Brachial artery Femoral artery  Brachial Pulmonary vein Pulmonary circulation is very complaint ∴ Can be artery used as an indirect measure of left atrial pressure. Why would you Right measure left atrial ventricle pressure??  Generating a pressure-volume loop (PV-loop) A: Pressure = 10mmHg ; Volume =75ml B: Pressure = 130mmHg ; Volume =20ml B A  Phases and events in the PV-loop Point A: Completion of the diastolic filling phase. A to B: Isovolumetric contractile phase (No movement of blood from the ventricle ) Point B: Opening of the aortic valve, this occurs when the pressure in the left ventricle becomes higher than the pressure in the aorta. B to C: Ejection phase (blood travels down its pressure gradient from the left ventricle into the aorta) Point C: Ventricular pressure falls below aortic pressure as myocardial relaxation begins, causing aortic valve closure as blood begins to flow in a retrograde direction towards the left ventricle. C to D: Isovolumetric relaxation phase (Both the mitral and aortic valves are closed and ventricle relaxes, substantial decrease in pressure) Point D: Completion of relaxation and the mitral valve opens again. D to A: Diastolic filling phase occurs passively as blood flows down its pressure gradient from the left atrium into the left ventricle.  Common measurements collected from the PV-loop Point 1: End-Diastolic Volume (EDV); this shows the volume of blood which has filled the left ventricle during the diastolic filling phase. Synonymous with ‘preload’. Point 2: Represents what is known as the ‘afterload’ of the heart. Point 3: End-Systolic Volume (ESV); this shows the volume of blood remaining in the ventricle after the ejection phase. Other measurements which can be calculated: Stroke volume (SV): The difference between ESV and EDV Cardiac output (CO): HR * SV Ejection fraction (LVEF): Calculated using SV as a proportion of EDV (SV/EDV*100). This is an important measure for tracking pumping function of the left ventricle and in a healthy heart EF is usually fifty five percent or higher. Stroke Work (SW): The area within the loop can be calculated (shaded blue) and represents work completed by the left ventricle to eject blood into the aorta each cardiac cycle.  Ventricular pressure volume relations End-systolic pressure-volume relationship (ESPVR): Total pressure able to be generated, by passive tension and active contraction during systole for a given inotropy. End-diastolic pressure-volume relationship (EDPVR): Resting Tension due to stretch during diastolic filling (preload) PV-loop cannot cross these boundaries at a given inotropy ESPVR becomes steeper with increased inotropy  Factors Influencing Ventricular Performance 1. Preload 2. Afterload 3. Inotropic state (Contractility) 4. Heart rate  1. Preload End diastolic volume (EDV) represents the extent to which myocardial sarcomeres are stretched at the time contraction commences. EDV is referred to as Preload - It sets the resting tension of the muscle fibres prior to contraction If preload (EDV) is increased – Stroke volume increases – Velocity of ejection increases – Causes of increased EDV? Renal Failure  TPR  Muscular contraction (Particularly deep leg veins)  Ventricular pressure vs volume dynamics Intra- Preload - Isolated heart Ventricular Pressure (mmHg) Afterload and 120 contractility remain constant What would happen if aorta occluded 1 beat? Volume  Ventricular pressure vs volume dynamics Intra- Preload - Intact changes Ventricular Pressure (mmHg) Aorta occluded 1 120 beat Increase LVP Increase EDV Volume Cardiac Output - Changes in preload Frank-Starling law of the heart – Stroke volume increases as cardiac filling increases Heart contracts more forcefully when it is filled more Increased muscle cell length increases sensitivity of myofilamants to Ca++ – Matches output of left and right sides – When more CO is needed, venous return increase will ensure stroke volume increase.  2. Afterload Afterload is an indirect representation of the tension that the left ventricular sarcomeres need to generate to overcome the resistance provided by aortic blood pressure. Aortic arterial pressure is referred to as Afterload Suddenly reduced – Stroke volume increases (ESV decreases) – Velocity of ejection increases Suddenly increased – Stroke volume decreases (ESV increases) – Velocity of ejection decreases  Ventricular pressure vs volume dynamics Intra- Afterload - Isolated heart Ventricular Pressure (mmHg) Preload and 120 contractility remain constant What would happen if sudden injection of noradrenaline? Volume  Ventricular pressure vs volume dynamics Intra- Afterload - Intact changes Ventricular Pressure (mmHg) TPR increased by 120 noradrenaline Increase LVP Increase EDV Volume  3. Contractility Heart intrinsic contractile performance (Independent of Preload and Afterload). Can be measured via ESPVR – Increased contractility (positive inotropic agents) Increased [Ca2+]I Adrenergic agonists (β1 receptors) Cardiac glycosides ( intracellular Ca2+) Changes in ion balances ( extracellular Ca2+ or Na +) – Decreased contractility (negative inotropic agents) Decreased [Ca2+]I Ca2+ channel blockers (Inhibit L-type Ca2+ channels) Changes in ion balances (Opposite to above)  Ventricular pressure vs volume dynamics Intra- Ventricular Pressure (mmHg) Increased 120 contractility Volume  Frank-Starling Curve Stroke Volume (ml) (related to muscle tension) 200 Sympathetic stimulation Increase contractility 100 Shortening  Increase in afterload Increase in preload End Diastolic Volume (ml) (related to muscle length) 100 200 4. Effect of heart rate on stroke volume Ventricular Filling Atrial Contraction 80 75 / min Volume (ml) Ventricular Emptying 40 0 0 0.2 0.4 0.6 0.8 Time (s) 4. Effect of heart rate on stroke volume Ventricular Filling Atrial Contraction 80 Volume (ml) Ventricular 100/ min 40 75 / min 0 0 0.2 0.4 0.6 0.8 Time (s) Determinants of Heart Performance All factors operate simultaneously May vary in different directions  Determinants of Heart Performance Preload Change in venous return = immediate change in performance. Eg. Posture change. Changes in right ventricle lead to changes in left ventricle (short delay) Atrial stretch important in strenuous exercise With pathologically slow HR, prolonged filling = EDV (Athletes heart/Cardiomegaly)  Role of atria in exercise Rest Strenuous Exercise Ventricular pressure With very fast heart rate, diastole is shortened more than systole. Atrial contraction plays a greater role in late ventricular filling.  Determinants of Heart Performance Afterload Autonomic changes effect both BP and heart rate / force Drug induced changes in aortic pressure Vasoconstrictor = – decreased SV – restored by increased EDV  Law of Laplace Wall stress is the formal definition of afterload (closely related to aortic pressure) Tension = Ventricular pressure Wall thickness = Hypertrophy or dilation Wall stress = tension wall thickness Force acting against myocardial cells r P Pressure overload (eg Aortic stenosis) = increased tension Concentric hypertrophy (without dilation) Normalises stress by spreading over greater X-sect area Wall stress = tension wall thickness Volume overload (eg Aortic or mitral insufficiency) = increased EDV Eccentric hypertrophy (with dilation) Leads to increased wall stress  Determinants of Heart Performance Contractility Sympathetic or adrenergic activity 1. Noradrenaline activates β1-adrenoceptors - increasing Ca2+ permeability 2. Increased HR**(Bowditch effect – the staircase effect) L-type channels become more permeable to Ca2+ and time spent in diastole  Therefore, Ca2+i accumulates as there is more entering and less time to remove it, leading to  contractile force 3. Increased muscle cell length ( EDV) increased sensitivity of myofilamants to Ca2+  Revision Question Q1: A young adults moves from standing to a supine body position. Which of the following best describes the effect on stroke volume? A. Venous return reduces, EDV reduces, HR increases B. Venous return increases, EDV increases, HR decreases C. Afterload increases, ESV increases, HR increases D. Afterload decreases, ESV decreases, HR decreases E. Afterload stays the same and does not influence stroke volume  Pathological Effects 250 200 LV Pressure 150 100 50 0 0 50 100 150 200 250 300 350 400 450 LV Volume  Functional Cardiac Pathophysiology Heart failure (Left and Right Side) Valve disorders (Stenosis or insufficiency) Cardiac hypertrophy (Eccentric or Concentric) Myocardial infarction Disorders of cardiac rhythm Myocardial ischaemia Cardiac hypertrophy Infarction  Pathological Effects LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Mitral valve stenosis (rheumatic fever) Restrictive filling of LV (obstruction to blood flow in diastole) Elevated LA pressure, volume, R heart pressures Reduced EDV Reduced stroke volume Reduced systolic pressure  Pathological Effects LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450  LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Mitral valve insufficiency (papillary dysfunction, rheumatic deformity, ventricular enlargement) Regurgitation (LV - LA backflow) LA has elevated pressure and volume Forward output ≠ total output Volume overload (regurgitated + venous return) EDV = stretch = dilated ventricle Isovolumetric contraction period absent Ejection fraction  acutely (Frank-starling stretch) but then  when ventricle dilates  LV Volume Acute changes: 250 Normal LA size but high LA 200 pressure (LA not compliant) LV Pressure  pulmonary congestion and 150 oedema Frank-starling compensation 100 can counteract  EDV and 50 maintain SV 0 Chronic changes 0 50 100 150 200 250 300 350 400 450 (compensated): Increased LA size  normal LA and pulmonary pressure. Eccentric LV hypertrophy   SV but low forward movement (decompensated): LV dilates and muscle deteriorates therefore frank- starling effect  and blood pools in LV   SV  Pathological Effects LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Aortic valve stenosis (age, rheumatic heart disease) Obstructed outflow Increased pressure required for ejection Pressure overload Reduced ejection fraction Chronic compensation: Concentric hypertrophy (some ventricular dilatation) Elevated ESP and EDP  Pathological Effects LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Clinical manifestations: Angina (mismatched MVO2 due to increased muscle mass and increased compression of coronary arteries) Congestive heart failure??  LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Aortic valve stenosis + insufficiency ( rheumatic, congenital, aortic aneurism) Pressure overload Regurgitation = volume overload (regurgitated + venous return) Ventricular dilatation (some hypertrophy) Elevated end diastolic pressure Widened pulse pressure Can you identify each pathological condition? 250 200 LV Pressure 150 100 50 0 0 50 100 150 200 250 300 350 400 450 LV Volume Cardiomyopathy  Cardiomyopathies Hypertrophic Dilated Most common Pressure Overload Chamber enlargement and systolic Thickened ventricle and diastolic dysfunction dysfunction (relaxation) Volume Overload/ Tissue Death – Familial/Genetic (SCD in athletes) – Idiopathic – Hypertension – Familial/Genetic – Valvular Stenosis (Aortic) – Inflammatory Infections & non-infectious Restrictive – Toxic Least common Alcohol and chemotherapy Walls are rigid and heart is – Metabolic restricted from stretching and Hyperthyroid & ↓ Ca+ Phos filling – Neuromuscular  fibrotic tissue in ventricle wall Muscular Dystrophy  Pathological Effects LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Myocardial Infarction (Hypertrophic) Damaged, non functioning wall region Hypertrophy of viable myocardium Increased EDV (normal VR +  ESV) Reduced ejection fraction Reduced systolic pressure (contractility impaired)  Pathological Effects LV Volume 250 LV Pressure 200 150 100 50 0 0 50 100 150 200 250 300 350 400 450 Idiopathic Dilated Cardiomyopathy Dilated left ventricle (no compensatory thickening) Increased EDV & ESV Reduced SV Reduced EF  Revision Question Q2: The P-V loop shown in green (where black is normal), is due to which of the following pathological conditions? A. Myocardial infarction B. Mitral valve stenosis C. Mitral valve insufficiency D. Aortic valve stenosis E. Aortic valve insufficiency  Heart Failure The hearts inability to pump blood and oxygen to the needed parts of the body, including itself. Termed “Cardiomyopathy”. Usually a result of decreased systolic function of the left ventricle due to loss of muscle or decreased contractility.  Incidence of HF in Western population  Myocardial Oxygen Consumption (MVO2) HEART RATE INOTROPIC STATE SYSTOLIC PRESSURE SHORTENING wall tension EXTENT < 0.05% Activation energy Basal Metabolism 19% Anatomical view of the coronary arteries Coronary arteries supply the heart with the blood perfusion it needs to maintain contractile work Boron WF & Boulpaep EL , Medical Physiology, Saunders, Philadelphia, 2003 Extravascular compression and partially blocked arterial entrance impairs coronary blood flow during systole. Therefore perfusion mainly occurs during diastole. Boron WF & Boulpaep EL , Medical Physiology, Saunders, Philadelphia, 2003 Clinical syndromes in heart failure (BACKWARD FAILURE) – inadequate venous emptying * (FORWARD FAILURE) – inadequate ejection  Types ❖ Left Ventricular Failure – Causes blood to build up in lungs causing dyspnoea 2/3 caused by systolic failure, 1/3 caused by diastolic failure ❖ Right Ventricular Failure – Can follow causing oedema of the legs and abdomen ❖ Congestive Heart Failure – Combination of the two to where BP is very low, the body retains salt and fluid, which leaks out into surrounding tissue. What would you expect to happen to jugular venous pressure?  Causes Idiopathic (unknown) Valvular Dysfunction Viral Heart Attack Severe Hypertension Alcohol/Drug Use (alters Ca2+ flux) Iron Overload ( oxidation) Chemotherapy Agents  Implications Increased left ventricular filling pressures Increased pulmonary and ventricular venous pressure Secondary organ damage/changes (Kidney, liver, lungs) Altered muscle metabolism (Anaerobic) Impaired vasodilation ( SNS) Renal insufficiency (Salt & water retention)  Signs & symptoms Dyspnoea – worsens w/exertion, lying down (orthopnoea), or at night (paroxysmal nocturnal dyspnoea). Severe breathlessness at rest is termed “Pulmonary Oedema”. Rapid breathing (tachypnoea) Oedema (+10lbs/week) Fatigue Anorexia (cachexia – wasting) Cyanosis and/or Pallor Sweating Anxiety Decreased exercise tolerance Dizziness Sinus tachycardia  Pharmacological treatment Beta-Blockers (MVO2) Digitalis (cardiotonic -  contraction by  calcium ions in heart muscle to help kidneys resume normal functioning) Diuretics -  water and salt reabsorption in the kidneys - Lasix (furosemide) & Thiazides ACE Inhibitors (vasodilators) Aspirin  Surgical treatment Muscle transposition, muscle/scar resection and left ventricular cross-sectional reduction. Valve replacement (pig, mechanical, cadaver) Myocardial laser reperfusion External pumps/LVAD Heart transplant  Cardiac hypertrophy Adaptive process to enable the heart to maintain function under demanding conditions. – Adjustments of size – Length-tension relationship – Adjustments of geometry – Adaptation occurs to attempt to maintain wall stress  Pressure overload – Acute changes Increased – LV systolic pressure – LV radius – LV diastolic volume (Normal VR +  ESV) No change in wall thickness What would happen to wall stress? Wall stress = tension wall thickness  Compensatory response to pressure overload – Chronic changes Sustained – High LV systolic pressure – Enlarged LV radius Increased – Wall thickness (Hypertrophy) Normalised – LV diastolic volume (partial) – Wall stress (partial) Wall stress = tension wall thickness *Augmented ventricular working capacity  Cardiac failure Sustained – High LV systolic pressure – Enlarged LV radius (dilation – Wall thickness ) – Myocyte degradation (Frank-Starling ) Increased – LV diastolic volume – Wall stress *Diminished ventricular working capacity  Acute adjustment Compensatory Cardiac Normal to afterload Hypertrophy Failure 300 300 300 300 Pressure (mmHg) Pressure (mmHg) Pressure (mmHg) Pressure (mmHg) 200 200 200 200 100 100 100 100 0 0 0 0 0 50 100 150 200 0 50 100 150 200 0 50 100 150 200 0 50 100 150 200 Volume (ml) Volume (ml) Volume (ml) Volume (ml) Sarcomeres Stretch Multiply Stretch Cells per unit tissue weight Heart weight and myocyte number Neurohumoral mechanisms in Heart Failure (short term) vasoconstriction (TPR ) MAP tachycardia contractility (CO ) Vasoconstriction Neurohumoral mechanisms in Heart Failure (long term) Exercise Stress Test Heart Failure: Significant decrease in maximal cardiac output reduced maximal exercise capacity. Impaired Contractility IncreasedAfterload Myocardial infarction Aortic stenosis Trans myocardial ischemia Uncontrolled hypertension Chronic volume overload Dilated cardiomyopathy Systolic Dysfunction Left Side Heart Can you relate these changes seen in HF with the changes to Failure wall stress? Diastolic Dysfunction Impaired Ventricular Relaxation Left Ventricular Filling Obstruction Left ventricle hypertrophy Mitral stenosis Hypertrophic cardiomopathy Pericardial constriction Restrictive cardiomyopathy Trans myocardial ischemia  Revision Question Q3: In acute, short term heart failure, of the following neuro-humoral changes occurs? A. Decreased TPR B. Increased renin production C. Bradycardia D. Vasodilation E. Decreased SNS drive.  Revision Question A. Aortic incompetence B. Aortic stenosis C. Atrial septal thickening D. Mitral incompetence E. Mitral stenosis F. Pulmonary incompetence G. Pulmonary stenosis H. Tricuspid incompetence I. Tricuspid stenosis J. Ventricular septal thickening Select from the list which condition best fits the immediate physiological outcome for the heart; Q1. Increased right atrial pressure Q2. Increased left ventricular isovolumic pressure Q3. Reduced left ventricular EDV