Cardiovascular Physiology L05 (Cardiac Output) - Summer 2024 PDF

CARDIOVASCULAR PHYSIOLOGY 5. Cardiac output Andre Azevedo, DVM, MSc Assistant Professor of Veterinary Physiology [email protected] Learning objectives for this lecture Describe stroke volume, ejection fraction,...

CARDIOVASCULAR PHYSIOLOGY 5. Cardiac output Andre Azevedo, DVM, MSc Assistant Professor of Veterinary Physiology [email protected] Learning objectives for this lecture Describe stroke volume, ejection fraction, and cardiac output Understand intrinsic and extrinsic factors affecting cardiac output Understand the Frank-Starlin mechanism Describe how the ANS influences cardiac heart rate and contractility Understand the most important adrenergic and cholinergic receptors of the heart and their actions  FYI Clinical correlation ECHOCARDIOGRAPHY EXAM LVIDd: 68mm (33.0 – 46.6) LVIDs: 55.9mm (18.8 – 29) Shortening fraction: 17.79% (33 – 46%) EDV: 113ml ESV: 72,28ml Ejection fraction: 36.04% (>50%) Regulation of heart pumping The function of the ventricles is described by 3 parameters: 1. STROKE VOLUME 2. EJECTION FRACTION 3. CARDIAC OUTPUT  Stroke volume Is the volume of blood (mL) ejected out of the left ventricle during each systolic cardiac contraction Is the difference between: the volume of blood (mL) in the ventricle BEFORE EJECTION (END-DIASTOLIC VOLUME) and the volume (mL) remaining in the ventricle AFTER EJECTION (END-SYSTOLIC VOLUME) Stroke volume (ml) = End-diastolic volume – End-systolic volume  Ejection fraction Is the fraction (%) of the end-diastolic volume that is ejected in one stroke volume Describes the effectiveness of the ventricles in ejecting blood Normally around 60% (0.6) It is an indicator of contractility The increase in ejection fraction reflects an increase in contractility The decrease in ejection fraction reflects a decrease in contractility Left ventricular ejection fraction = Stroke volume / End-diastolic volume Cardiac output Is the total volume of blood ejected by the left ventricle per unit time (mL/min) Depends on the volume ejected on a single beat (STROKE VOLUME) and the number of beats per minute (HEART RATE) Cardiac output varies widely with the levels of activity of the body Body metabolism Exercise Age Size of the body Cardiac output (ml/min) = Stroke volume (ml) x heart rate (beats/min)  Cardiac output Cardiac output can be increased only if SV increases, HR increases, or both increase To understand how the body controls cardiac output, we must understand how the body controls stroke volume and heart rate Cardiac output (ml/min) = Stroke volume (ml) x heart rate (beats/min) Factors affecting stroke volume The stroke volume can be increased only by increasing end-diastolic volume or decreasing end-systolic volume The stroke volume is affected by: 1. PRELOAD 2. CONTRACTILITY 3. AFTERLOAD Stroke volume (ml) = End-diastolic volume – End-systolic volume Factors affecting stroke volume 1. PRELOAD Is the pressure acting to stretch LV fibers at END-DIASTOLE The stretching of the cardiac myocytes before contraction Determines the resting length from which the muscle contracts Expressed in terms of LV END-DIASTOLIC PRESSURE or END-DIASTOLIC VOLUME Preload is mainly determined by A. DIASTOLIC FILLING B. VENOUS RETURN  Factors affecting stroke volume 1. PRELOAD (END-DIASTOLIC VOLUME/FIBER LENGTH) RECALL that for SKELETAL MUSCLE, there is an optimal resting muscle length at which MAXIMAL TENSION can be developed during a subsequent contraction When Skeletal muscle is longer or shorter than the optimal length, the subsequent contraction is weaker LENGTH-TENSION RELATIONSHIP OF SKELETAL MUSCLE  Factors affecting stroke volume 1. PRELOAD (END-DIASTOLIC VOLUME/FIBER LENGTH) For CARDIAC MUSCLE, the normal resting fiber length is less than optimal! An increase in fiber length increases the contractile force of the heart on the following systole LENGTH-TENSION RELATIONSHIP OF CARDIAC MUSCLE  Factors affecting stroke volume 1. PRELOAD (END-DIASTOLIC VOLUME/FIBER LENGTH) INFLUENCED BY DIASTOLIC FILLING AND VENUS RETURN The greater the extent of diastolic filling, the larger the end-diastolic volume, and the more the heart is stretched The more the heart is stretched, the longer the initial cardiac fiber length before contraction The increased length leads to a greater force of contraction and a greater stroke volume Factors affecting stroke volume This intrinsic relationship between the end-diastolic volume and stroke volume is known as the “FRANK-STARLING LAW” In honor to Otto Frank and Ernest Starling “The volume of the blood ejected by the ventricles depends on the volume present in the ventricle at the end of diastole” Frank-starling mechanism: The greater the heart muscle is stretched during filling, the greater is the force of contraction, and the greater the quantity of blood pumped into the aorta. Stroke volume increases as preload increases  Factors affecting stroke volume 2. CONTRACTILITY OR INOTROPISM Refers to the pumping ability of a ventricle The intrinsic ability of myocardial cells to develop force at a given cell length An increase in contractility leads to a more complete emptying of the ventricle during systole = DECREASE IN END SYSTOLIC VOLUME Consequently, INCREASE IN STROKE VOLUME Without the need to increase end-diastolic volume Stroke volume (ml) = End-diastolic volume – End-systolic volume Stroke volume increases as contractility increases Factors affecting stroke volume 2. CONTRACTILITY OR INOTROPISM Contractility is directly correlated with the intracellular calcium concentration The larger the inward calcium current and the larger the intracellular stores, the greater the increase in intracellular calcium and the greater the contractility Extrinsic factors increase contractility = POSITIVE INOTROPIC EFFECT SYMPATHETIC STIMULATION CATHECOLAMINES Factors affecting stroke volume 2. CONTRACTILITY OR INOTROPISM EPINEPHRINE AND NOREPINEPHRINE: Increase contractile force and velocity of contraction by stimulation of beta 1 adrenergic receptors Increase calcium influx and activation of Ryanodine receptors to further increase SR Calcium release Through protein phosphorylation of L-type calcium channels Speed up calcium accumulation in SR to allow faster cardiomyocyte relaxation Increase heart rate, stroke volume, and cardiac output Factors affecting stroke volume 3. AFTERLOAD Is the resistance that the ventricles must overcome to empty its content – The force opposing ejection The afterload for the left ventricle is the AORTIC PRESSURE When aortic blood pressure increases Stroke volume decreases End systolic volume/pressure increases Can also be raised by obstructions to flow (i.e. semilunar valve stenosis) Stroke volume decreases as afterload increases Factors affecting stroke volume 3. AFTERLOAD THE ANREP EFFECT - Russian physiologist Gleb von Anrep (1912) Allows myocardium to compensate for an increased end-systolic volume and decreased stroke volume that occurs when aortic blood pressure increases The initial increase in the contractile force of the ventricle is achieved through the Frank- Starling mechanism. If the increased afterload is maintained for 10-15 minutes, the force of contraction (inotropy) increases further (ANREP EFFECT) Increased release of Ca from sarcoplasmic reticulum  stronger muscle contraction Mediated by release of endothelin-1 and angiotensin II by cardiac cells in response to the continuous increased tension Without this effect, every increase in aortic blood pressure would create a drop in stroke volume and would compromise circulation to peripheral and visceral tissues Volume-pressure Diagram Increased preload Increased EDV Increased contractility Decreased ESV Increased afterload Stroke volume is measured by the width of Increased ESV the pressure volume loop  Factors affecting heart rate The HEART RATE is affected by the autonomic nervous system Sympathetic activity Parasympathetic activity Factors affecting HR - sympathetic Activation of SYMPATHETIC SYSTEM CNS PNS TARGET ORGAN In cardiac tissue, beta receptors predominate The location of beta 1 and beta 2 adrenergic receptors change depending on the species N2 = N N  Factors affecting HR - sympathetic Primarily Beta 1 adrenergic receptors are expressed in the heart G protein-coupled receptor that couples to Gs Stimulatory G protein – activates the cAMP pathway Norepinephrine is the primary endogenous agonist Released from postganglionic neurons Found in the SA node, AV, node and myocardial cells (atria and ventricles) Increase heart rate, stroke volume, and cardiac output Beta 1 receptor activation increases: the inward Na current in the pacemaker cell (Funny sodium channels) The inward Ca current in the pacemaker cell  Factors affecting HR - sympathetic Beta 2 adrenergic receptors are expressed in the arterioles of the coronaries G protein-coupled receptor that couples to Gs Stimulatory G protein - activates the cAMP pathway Epinephrine is the primary endogenous agonist Released from the adrenal gland Found in vascular smooth muscle Activation of cAMP pathway Cause vasodilation leads to smooth muscle relaxation Factors affecting HR - sympathetic When HR is increased, contractility also increases more APs per unit of time more total calcium entering the cell during the plateau phase more calcium accumulation by the SR Beta receptors: Enhance myocardial contractility (positive inotropic effect) Speed AV conduction (positive dromotropic effect) Increase heart rate (positive chronotropic effects) Dilate coronary arteries Factors affecting HR - parasympathetic Activation of the PARASYMPATHETIC SYSTEM CNS PNS TARGET ORGAN In cardiac tissue, M2 receptors predominate Factors affecting HR - parasympathetic M2 receptors are expressed in the heart G protein-coupled receptor that couples to Gi Inhibitory G protein - inhibit the cAMP pathway Acetylcholine is the endogenous agonist Released from postganglionic neurons Found in the SA node, AV node, and myocardial cells Inhibition of camp pathway (MAINLY ATRIA) decreases HR and cardiac output Slow down the discharge rate of the SA node, slow or block AV conduction and decrease atrial and, to a small extent, ventricular contractility  Factors affecting HR - parasympathetic There is little or no parasympathetic innervation of most vessels of the body M3 receptors on coronaries can respond to vagal tonus G protein-coupled receptor that couples to Gq Stimulates phospholipase C – DAG and IP3 – Calcium release activates eNOS and the production of NO Acetylcholine is the primary endogenous agonist Activation of camp pathway Released from postganglionic neurons leads to smooth muscle relaxation Found in vascular smooth muscle Cause vasodilation (minor effect) Reciprocal sympathetic-vagal activity PARASYMPATHETIC ACTIVITY predominates in the heart, but both systems act in a reciprocal manner Sympathetic activation increases HR, while parasympathetic activation decreases Blockade of sympathetic B1 receptors slightly decreases HR while blockade of parasympathetic M2 receptors substantially increases HR An increase in heart rate usually results from both the removal of vagal tone and an increase in sympathetic drive Reciprocal sympathetic-vagal activity Neurotransmitters from each system can affect the other division of the ANS Ach released from vagal endings reacts with presynaptic muscarinic receptors on sympathetic nerve endings to reduce the amount of norepinephrine released from sympathetic efferent terminals Parasympathetic innervation is sparse in the ventricles, but decrease in contractility is achieved if vagal tone increases in the presence of high concurrent sympathetic activity Cardiovascular Physiology Concepts, 3rd ed, Richard E. Klabunde, Wolters Kluer. Control of cardiac output - summary SYMPATHETIC ACTIVITY PRELOAD + CONTRACTILITY CIRCULATING CATHECOLAMINES AFTERLOAD PARASYMPATHETIC HEART STROKE ACTIVITY RATE VOLUME CARDIAC OUTPUT  FYI Clinical correlation ECHOCARDIOGRAPHY EXAM LVIDd: 68mm (33.0 – 46.6) LVIDs: 55.9mm (18.8 – 29) Shortening fraction: 17.79% (33 – 46%) EDV: 113ml ESV: 72,28ml Ejection fraction: 36.04% (>50%)  FYI Clinical correlation - DCM DILATED CARDIOMYOPATHY LVIDd: 68mm (33.0 – 46.6) LVIDs: 55.9mm (18.8 – 29) Shortening fraction: 17.79% (33 – 46%) EDV: 113ml ESV: 72,28ml Ejection fraction: 36.04% (>50%)  FYI Clinical correlation - DCM DILATED CARDIOMYOPATHY (DCM) A primary disease of the heart muscle (cardio = heart; myo = muscle; pathy = disease). Ventricles become weak and loses their ability to contract normally. Characterized by dilation of the ventricles with ventricular wall thinning. Decreased contractility  decreased SV  decreased cardiac output Dilated ventricle  AV valves don’t close correctly  left side heart failure  fluid accumulation (lungs) One of the most common acquired heart diseases in dogs. Signs: Exercise intolerance, lethargy, weakness, weight loss, collapse, pale gums, tachycardia, coughing, difficulty breathing. Cause: Several factors including nutritional, infectious, and genetic predisposition have been implicated. Breeds predisposed: Doberman Pinscher, Great Dane, Boxer, and Cocker Spaniel. Large and giant breeds are more commonly affected. Diagnosis: Echocardiography, thoracic radiography. Treatment: ??? (let’s think!) Prognosis: fair to poor – survival < 1 year. Treatment slows progression. Further information: https://www.vet.cornell.edu/hospitals/companion-animal-hospital/cardiology/canine-dilated-cardiomyopathy-dcm https://veterinarypartner.vin.com/default.aspx?pid=19239&id=4952598 https://www.msdvetmanual.com/circulatory-system/cardiomyopathy-in-dogs-and-cats/dilated-cardiomyopathy-in-dogs-and-cats Questions?