BMS 204 Cardiac Output Part 2 PDF

BMS 204: Cardiac output part 2 Dr Noha Lasheen Associate Professor of Physiology F A C U L T Y O F M E D I C I N E F a l l 2 0 2 4 By the end of this lecture, you should be able to:...

BMS 204: Cardiac output part 2 Dr Noha Lasheen Associate Professor of Physiology F A C U L T Y O F M E D I C I N E F a l l 2 0 2 4 By the end of this lecture, you should be able to: Recall cardiac output definition, primary factors and its regulation Illustrate in graphs effects of preload, afterload, contractility and heart rate on left ventricular loop Describe ventricular function curves and vascular(venous) function curves Outline the mechanisms of cardiac reserve and explain their limitation 1-Contrcatility (contractile state or inotropic state) It is the intrinsic ability of the cardiac muscle to do stroke work ( generate force). Normal contractility reflects:- 1. Healthy myocardium 2. Normal blood supply 3. Normal metabolism. Contractility is depressed in:- 1. Hypoxia, Hypercapnea & acidosis. 2. Myocardial infarction, viral myocarditis. 3. Intoxication by drugs.e.g. barbiturates. 4. Intrinsic depression ( may be due to down regulation of β-adrenergic receptors and associated signaling pathway and impaired calcium liberation from S.R  Sympathetic stimulation increase contractility (+ve inotropism). The cardiac muscle fiber contract with greater strength at any given length. When the strength of contraction ↑ without ↑ muscle fiber length ➔ more blood that normally remains in the ventricles is expelled = ↑SV & ↓ESV ➔ ↑ ejection fraction Parasympathetic stimulation depress contractility (-ve inotropism). This effect is direct on the atria and indirect on the ventricles. Effect of contractile state on stroke volume Effect of preload on stroke volume Effect of afterload on stroke volume 4- Heart Rate ↑ heart rate between 60-90 bpm➔ CO is unchanged due to decreased SV as a result of decreased ventricular filling time. In the range of physiologic tachycardia (100-160 bpm.), SV is increased due to:- 1. The +ve inotropic effect of increased heart rate. 2. +ve inotropic effect of sympathetic stimulation. 3. Venoconstrictor effect of sympathetic stimulation. With extreme changes in heart rate, CO is markedly decreased. +ve Inotropic Effect Of increased HR  Contractility Afterload Preload Myocardial fiber shortening SV HR CO PR ABP  Blood Experiment Observation Conclusion Reservoir Elevation of blood ↑EDV ↑muscle reservoir ↑SV length→↑force of ↑ESV contraction Lung Heterometric regulation Elevation of aortic ↑EDV ↑muscle P pressure ↑SV length→↑force of ↑ESV contraction A Heterometric regulation Maintained ↓ESV Homometric elevation of blood regulation reservoir or Maintained elevation of aortic pressure  Heterometric Homeometric Stimulus ↑EDV ↑Intraventricular pressure Basis Frank-Starling Increased contractile mechanism state Onset Early onset Delayed Duration Short lived Prolonged Mechanism Muscle length approximates Metabolic change optimum length Limit Certain level of EDV Calcium availability  Extrinsic Regulation of CO It acts on SV & HR It is homometric & not heterometric = It occurs at the same EDV. Extrinsic regulation involves :- 1. Physiologically acting extrinsic factors (neural factors &hormonal factors). 2. Humorally mediated extrinsic factors ( drugs & ions). A)-Physiologically acting Extrinsic factors 1. Sympathetic Stimulation 2. Parasympathetic stimulation 3. Circulating adrenal neurohormones B)-Humorally mediated extrinsic factors 1. Drugs acting on cAMP 1. Catecholamine, β- agonists increase CO ( via activation of c AMP) 2. Caffeine & theophylline increase CO ( via inhibition of phosphodieterase enzyme which causes breakdown of cAMP) 3. B-blockers decrease CO. 2. Glucagon has strong +ve inotropic effect & weak chronotropic effect. act on its own receptors. 3. Drugs acting on intracellular calcium (Digitalis, Nifadipin). 4. Direct myocardial depression ( barbiturates, hypoxia, hypercapnia, acidosis) Ventricular function curves 1. The ventricular function curves or Starling curves are a group of curves, all describing the relation between preload (diastolic function) & cardiac output (systolic function). 2. The preload (independent factor) is represented on the horizontal scale by right atrial pressure (RAP); while CO (dependent factor) is represented on the vertical scale. 3. Each individual curve represents a Frank Starling relationship (heterometric regulation). With increase in RAP, the CO is increased. 4. Shift of the curve represents homeometric regulation or change in contractility ➔the CO became different at the same EDV. Ventricular function curves 5. When the curve is shifted to the left (& upward): CO increases at any RAP meaning that increased contractility (+ ve inotropic effect) ➔ CO became higher at any degree of ventricular filling (at any EDV). The most important of shift to the left is sympathetic stimulation or circulating catecholamines 6. When the curve is shifted to the right (& downward), the CO decreases at any RAP this means a decreased contractility (-ve inotropic effect) ➔CO is less at any ventricular filling (at any EDV). The cause: vagal stimulation or myocardial depressant (-ve inotropic) factors. Heart failure represents an extreme case of shift to the right. Venous return Curve 1. The venous return curve (=vascular function curve) describes the relationship between venous return (VR = the inflow to the heart from the vascular system) & the RAP. 2. The RAP is represented on the horizontal scale, while the VR is represented on the vertical scale. 3. The driving force of venous return is equal to the difference between the mean circulatory pressure (MCP) & the central venous pressure (CVP or RAP): Force of VR = MCP - RAP Venous return Curve Venous return Curve 4. Mean Circulatory Pressure (MCP = 7 mm Hg) is the systemic filling pressure = the relation between blood volume & capacity of CVS. In the absence of the heart function, e.g. when the heart is stopped experimentally, MCP is equal in the entire CVS. -In the living body the MCP is very close or identical to the peripheral venous pressure (PVP). -Central Venous Pressure (CVP = 0 to 5 mm Hg) is the pressure in great veins at their entry to the heart, & is equal to RAP. 5. MCP is increased when blood volume is increased (hypervolemia) or when the capacity of CVS is diminished (venoconstriction)➔ VR is increased. MCP decreases in hypovolemia & venodilation ➔ VR is decreased. Venous return Curve 6. When ↑contractility ➔ ↓RAP ➔ ↑ VR due to the increased driving force [=MCP- RAP). On the contrary when contractility is depressed, RAP rises & VR is reduced. If the heart is arrested, RAP becomes equal to MCP ➔the driving force of VR is zero ➔no VR & no CO 7. With more negative RAP, VR remains constant (as indicated by the horizontal part of the curve) because of the gradual collapse of venous walls as they enter the thoracic cavity from higher pressure abdominal cavity. Cardiac Reserve is the ability of the heart to augment its CO in order to satisfy the increased body demands. It is the difference between maximal and basal cardiac output Or the difference between basal and maximal cardiac work Example: the cardiac output under maximal performance is 35 L / min. and during basal conditions is 5 L / min. ➔ the Cardiac Reserve = CO (max) - CO (basal) = 35 - 5 = 30 L I min Cardiac Reserve Mechanisms (Through, increases in the determinants of CO; HR & SV). I - Short -lived Mechanisms: Sudden & fast ↑ in CO to meet moment-to-moment increases in demands. All these mechanisms are initiated & maintained by graded ↑ in VR A. Increases In CO Within The Permissive Limit (~12 L / min): 1- HR increases from basal value (60 bpm) up to the value of intrinsic pacemaker frequency (~90 bpm) by canceling of inhibitory vagal tone (Bainbridge reflex) but does not involve sympatho-adrenal stimulation. 2- SV increases by intrinsic regulation upon increased VR & EDV, first by heterometric regulation & then homeometric regulation if prolonged for more than 2 minutes (at the same EDV) ➔SV is increased by the decrease in ESV B. Increases In CO Beyond The Permissive Limit: These are extrinsic mechanisms that depending on adrenergic support both sympathetic stimulation & circulating catecholamines. These extrinsic mechanisms are life saving since they can increase CO to meet the moment-to-moment increases in body demands beyond the permissive limit of the heart. They are determined by the ability of the heart to respond to beta- adrenergic stimulation. 1- HR reserve mechanism: Sympatho-adrenal stimulation exerts a +ve choronotropic effect & HR can be raised up to 180 bpm. 2- SV reserve mechanism: Sympatho-adrenal stimulation exerts a +ve inotropic effect. It acts at the same EDV & SV is increased by the decrease in ESV (may reach to 30 ml or less). II- Long - Lasting Mechanisms: Slow and gradual mechanisms, which are only intrinsic: either by 1- Dilatation (depends on Frank-Starling relationship). In volume overload as in cases of aortic valve incompetence, ventricular septal defect (VSD) & advanced congestive heart failure. In order to increase SV the heart has to increase its EDV 2- Hypertrophy in pressure overload, as in hypertension or aortic valve stenosis. In order to overcome the excessive resistance, LV has to increase the thickness of its wall (LV hypertrophy). Cardiac hypertrophy and cardiac diltation Limitations Of Cardiac Reserve 1] Increased CO within permissive limit (less than 12 L /min) has no limitation. 2] Extrinsic mechanisms depending on adrenergic support are limited by the stores of norepinepherine & responsiveness to beta-adrenergic stimulation. 3] Heart rate increases up to 180 bpm, if more the CO becomes reduced due to decreased ventricular filling ➔↓SV - Excessive rise in HR increases the workload & the oxygen consumption, while it decreases coronary blood supply to the ventricles. Limitations Of Cardiac Reserve 4] Excessive increase in EDV will result in overstretch ; beyond the limit of Starling, with diastolic dysfunction & extra needs of oxygen. 5] In excessive increases in contractility, the ESV decreases to very low values ➔ injury of the heart (athlete heart lesion). 6] Hypertrophy, if it exceeds certain limits ➔ ↓blood supply to the ventricle because blood vessels of the myocardium do not increase to the same extent as the muscular elements increase. Reserve mechanism Advantage Limitations Heart rate Help increasing cardiac output 1-Decreased ventricular filling 2-Increased O₂ consumption while coronary blood flow is decreased Excessive increase in EDV Help filling of the ventricle with 1-The force of contraction decrease due (i.e. dilatation) more blood in volume load to overstretch 2-Diastolic dysfunction 3-increased wall tension and increased O₂ consumption Excessive increase in Increase stroke volume and cardiac Excessive decrease in ESV which might contractility output injure the heart (athlete heart) Excessive hypertrophy Generation of more intraventricular Blood capillaries in the myocardium do pressure to overcome pressure load not increase proportionately to the with less O₂ cost. muscle leading to diastolic dysfunction Heart failure (HF) It is the inability of the heart to deliver the adequate cardiac output (CO) provided that there are normal filling conditions. If the needs were abnormally high: high output failure, as in fever & thyrotoxicosis. If the needs were normal: low output failure as in myocardial infarction. Mechanism of low cardiac output in heart failure: A. Systolic Dysfunction: In patients with myocardial infarction, the contractility (inotropic state) is depressed In moderate HF, the Ejection Fraction (EF) may be within normal range during rest (about 50 %), but the patient cannot raise it by exercise. But in more severe cases of HF, EF is reduced from about % 65 to 'as low as 20 % or even less. Mechanism of low cardiac output in heart failure: B. Diastolic Dysfunction: In patients with hypertension & some forms of hypertrophy & cardiomyopathy, even if systolic function is not impaired, ventricular compliance is decreased. The EDP is raised shifting the pressure- volume loop upward & to the left ➔ the SV is reduced & EF is even reduced more. Effects of heart failure: 1)Forward failure: the heart is unable to pump sufficiently ➔↓CO In moderate HF, CO is normal during rest & decrease during exercise; with progress of HF, CO becomes decreased, also, during rest. 2)Backward failure: the heart is unable to pump out all its venous return ➔the venous pressure is raised (CVP may reach to 20 mm Hg or more), and the organs behind become congested ➔CHF: congestive heart failure). In left sided heart failure (LHF), there is congestion in the lungs & pulmonary oedema; while on the right side (RHF) there is congestion in the viscera & oedema in the lower limbs. Types & causes of heart failure: 1. Primary Myocardial Failure: The myocardium itself is suddenly affected, while there was no disease in the heart. The most common cause is myocardial infarction, but also drug toxicity & viral myocarditis are possible causes. 2. Secondary Cardiac Failure: The heart was not normal previously and the mechanisms of cardiac reserve are operating but went beyond limits. a- Volume overload: (as in cases of semilunar valve incompetence, VSD). With overstretch & increase of EDV, diastolic compliance is decreased & EDP rises. b- Pressure overload: (as in cases of hypertension and semilunar valve stenosis). c- Rapid arrhythmias: (as in cases of persistent tachycardia, AF & VF). Physiological basis of treatment: Consider activity, meals & temperature, in order to decrease the demands. Digitalis: to improve inotropic state. Diuretics: to reduce congestion & oedema & to limit the increase in blood volume, ventricular filling and dependence on Frank Starling Relationship. Consider the use of -ve afterload (in cases of pressure overload) & -ve preload (in cases of volume overload). In secondary heart failure: treatment of the primary cause. References: Ganong’s Review of Medical Physiology. Kim E. Barrett (editor), 26th edition, 2019. Lange Basic Science Guyton and Hall Textbook of Medical Physiology (Guyton Physiology) 14th Edition, ELSEVIER, USA Fox, Stuart Ira. Human physiology / Stuart Ira Fox. — 12th ed. THANK YOU