2Outline Overview of heart anatomy and function Cardiac cycle Volume-‐Pressure Diagram Cardiac Output and Venous Return Regulation of Cardiac Output
3Learning Objectives Describe the cardiac cycle by explaining Fig. 9-6 in Guyton and HallAnalyze ventricular pumping with a volume ‐ pressure diagramUnderstand cardiac output and venous return - quantitatively know cardiac outputKnow how cardiac output is regulated - Frank- Starling mechanism and autonomic regulation
4Cardiovascular System Note, right side is the right side of the person or animal.Two pumps in the heart:Right side pumps blood through the lungs Left side through the peripheral organsEach side has an atrium and a ventricleAtrium is a primer pump for the ventricle Ventricle supplies the main pumping force
5Heart AnatomyAtrioventricular valves: tricuspid (right) and mitral (left) Semilunar valves: pulmonary (right) and aortic (left)
6Cardiac Cycle The cardiac cycle includes the events that occur from the beginning of one heartbeat to the beginning of the nextThe cardiac cycle consists of two periods:- Diastole - period of relaxation when the heart fills with blood- Systole - period of contraction
7Diastole: Passive ventricular filling. The AV valves open and Beginning just after aventricular contractionSemilunarvalves closedAV valvesopenedDiastole: Passive ventricular filling. The AV valves open andblood flows into the relaxed ventricles, accounting for most of theventricular filling.
8Diastole: Active ventricular filling. Semilunarvalves closedAV valvesopenedDiastole: Active ventricular filling.Semilunarvalves closedAV valvesopenedDiastole: Passive ventricularfilling.
9Semilunarvalves closedAV valvesopenedDiastole: Active ventricular filling. The atria contract and complete ventricular filling.
10Systole: Period of isovolumic contraction. Semilunarvalves closedAV valvesclosedSystole: Period of isovolumic contraction.Semilunarvalves closedAV valvesopenedDiastole: Active ventricular filling.
11Semilunarvalves closedAV valvesclosedSystole: Period of isovolumic contraction. Ventricular contraction causes the AV valves to close, which is the beginning of ventricular systole. The semilunar valves were closed in the previous diastole and remain closed during this period.
12isovolumic contraction. ejection. SemilunarSemilunarvalves openedvalves closedAV valves closedAV valves closedSystole: Period ofSystole: Period ofisovolumic contraction.ejection.
13Semilunarvalves openedAV valvesclosedSystole: Period of ejection. Continued ventricular contraction pushes blood out of the ventricles, causing the semilunar valves to open.
14Systole: Period of ejection. Semilunarvalves openedAV valvesclosedSystole: Period of ejection.Semilunarvalves closedAV valvesclosedDiastole: Period of isovolumic relaxation.
15Semilunarvalves closedAV valvesclosedDiastole: Period of isovolumic relaxation. Blood flowing back toward the relaxed ventricles causes the semilunar valves to close, which is the beginning of ventricular diastole. Note that the AV valvesclosed, also.
19The Cardiac CycleCardiac cycle refers to all events associated with blood flow through the heart from the start of one heartbeat to the beginning of the nextDuring a cardiac cycleEach heart chamber goes through systole and diastoleCorrect pressure relationships are dependent on careful timing of contractions
20Phases of the Cardiac Cycle Atrial diastole and systole -Blood flows into and passively out of atria (80% of total)AV valves openAtrial systole pumps only about 20% of blood into ventriclesVentricular filling: mid-to-late diastoleHeart blood pressure is low as blood enters atria and flows into ventricles80% of blood enters ventricles passivelyAV valves are open, then atrial systole occursAtrial systole pumps remaining 20% of blood into ventricles
21Phases of the Cardiac Cycle Ventricular systoleAtria relaxRising ventricular pressure results in closing of AV valves (1st heart sound – “lubb”)Isovolumetric contraction phaseVentricles are contracting but no blood is leavingVentricular pressure not great enough to open semilunar valvesVentricular ejection phase opens semilunar valvesVentricular pressure now greater than pressure in arteries (aorta and pulmonary trunk)
22Phases of the Cardiac Cycle Ventricular diastoleVentricles relaxBackflow of blood in aorta and pulmonary trunk closes semilunar valves (2nd hear sound - “dubb”)Dicrotic notch – brief rise in aortic pressure caused by backflow of blood rebounding off semilunar valvesBlood once again flowing into relaxed atria and passively into ventricles
23Normal Volume of Blood in Ventricles After atrial contraction, ml in each ventricle (end-diastolic volume)Contraction ejects ~70 ml (stroke volume output)Thus, 40-50 ml remain in each ventricle (End‐ systolic volume)The fraction ejected is then ~60% (ejection fraction)
24Left Ventricle Volume-‐Pressure Curve Be able to use these pressureand volume valuesAortic valve closesAortic valve opensMitral valve opensMitral valve closesEnd-systolic volumeEnd-diastolic volume
25Preload and AfterloadPreload - tension on muscle when it begins to contract (end-diastolic pressure)Afterload - load against which the muscle exerts its contractile force, which is thepressure in the artery leading from theventricle. Phase III on volume-pressurediagram
26Cardiac Output and Venous Return Cardiac output is the quantity of blood pumped into the aorta each minute.Cardiac output = stroke volume x heart rateVenous return is the quantity of blood flowing from the veins to the right atrium.Except for temporary moments, the cardiac output should equal the venous return
27Normal Cardiac Output Normal resting cardiac output: - Stroke volume of 70 ml- Heart rate of 72 beats/minute - Cardiac output ~ 5 litres/minuteDuring exercise, cardiac output may increase to > 20 liters/minutesYou should be able to get stroke volume and heart rate from volume-‐pressure curves andECG recordings, respectively
28Cardiac OutputStroke Volume = the vol of blood pumped by either the right or left ventricle during 1 ventricular contraction.SV = EDV – ESV70 = 125 – 55CO = SV x HR5,250 = 70 ml/beat x 75 beats/minCO = 5.25 L/min
29Cardiac Output Regulation of Stroke volume Preload: Degree of stretch of heart muscle (Frank-Starling) – greatest factor influencing stretch is venous return (see Below)Contractility – Strength of contractionIncreased Ca2+ is the result of sympathetic nervous system
31Cardiac Output Other chemicals can affect contractility: - Positive inotropic agents: glucagon, epinephrine, thyroxine, digitalis.- Negative inotropic agents: acidoses, rising K+, Ca channel blockers.Afterload: Back pressure exerted by arterial blood.Regulation of Heart RateAutonomic nervous systemChemical Regulation: Hormones (e.g., epinephrine, thyroxine) and ions.
32Regulation of Cardiac Output Frank-Starling Mechanism -‐ Cardiac output changes in response to changes in venous return.Autonomic control -‐ Control of heart rate and strength of heart pumping by the autonomicnervous system.
33Chemical Regulation of the Heart The hormones epinephrine and thyroxine increase heart rateIntra- and extracellular ion concentrations must be maintained for normal heart function
34Regulation of Stroke Volume SV: volume of blood pumped by a ventricle per beatSV= end diastolic volume (EDV) minus end systolic volume (ESV); SV = EDV - ESVEDV = end diastolic volumeamount of blood in a ventricle at end of diastoleESV = end systolic volumeamount of blood remaining in a ventricle after contractionEjection Fraction - % of EDV that is pumped by the ventricle; important clinical parameterEjection fraction should be about 55-60% or higher
35Factors Affecting Stroke Volume EDV - affected byVenous return - vol. of blood returning to heartPreload – amount ventricles are stretched by blood (=EDV)ESV - affected byContractility – myocardial contractile force due to factors other than EDVAfterload – back pressure exerted by blood in the large arteries leaving the heart
36Frank-Starling Law of the Heart Preload, or degree of stretch, of cardiac muscle cells before they contract is the critical factor controlling stroke volume; EDV leads to stretch of myocardium.preload stretch of muscle force of contraction SVUnlike skeletal fibers, cardiac fibers contract MORE FORCEFULLY when stretched thus ejecting MORE BLOOD (SV)If SV is increased, then ESV is decreased!!Slow heartbeat and exercise increase venous return (VR) to the heart, increasing SV.VR changes in response to blood volume, skeletal muscle activity, alterations in cardiac outputVR EDV and in VR in EDVAny in EDV in SVBlood loss and extremely rapid heartbeat decrease SV.
37Frank-Starling Law of the Heart Relationship between EDV, contraction strength, and SV.Intrinsic mechanism:As EDV increases:Myocardium is increasingly stretched.Contracts more forcefully.As ventricles fill, the myocardium stretches:Increases the number of interactions between actin and myosin.Allows more force to develop.Explains how the heart can adjust to rise in TPR.Figure 14.3
38Extrinsic Control of Contractility Strength of contraction at any given fiber length.Sympathoadrenal system:NE and Epi produce an increase in contractile strength.+ inotropic effect:More Ca2+ available to sarcomeres.Parasympathetic stimulation:Does not directly influence contraction strength.Figure 14.2
39Frank-Starling Mechanism The force of cardiac muscle contractionincreases as the muscle stretches, within limits.Due to more optimal overlap of actin and myosin filaments during stretch - same in skeletal muscleSo, with increase venous return and increased stretching, the force of contraction increases and the stroke volume increases.Moreover, stretching of the SA node increasing the firing rate of the pacemaker (increasing heart rate).
40Frank-‐Starling Summary: within physiological limits, the heart pumps all the blood that returns to it from the veins.Venous return increases when there is anincrease in the blood flow through peripheralorgans. So, peripheral blood flow is a major determinant of cardiac output
42Extrinsic Factors Influencing Stroke Volume Contractility is the increase in contractile strength, independent of stretch and EDVReferred to as extrinsic since the influencing factor is from some external sourceIncrease in contractility comes from:Increased sympathetic stimuliCertain hormonesCa2+ and some drugsAgents/factors that decrease contractility include:AcidosisIncreased extracellular K+Calcium channel blockers
43Effects of Autonomic Activity on Contractility Sympathetic stimulationRelease norepinephrine from symp. postganglionic fiberAlso, EP and NE from adrenal medullaHave positive ionotropic effectVentricles contract more forcefully, increasing SV, increasing ejection fraction and decreasing ESVParasympathetic stimulation via Vagus Nerve -CNXReleases AChHas a negative inotropic effectHyperpolarization and inhibitionForce of contractions is reduced, ejection fraction decreased
44Contractility and Norepinephrine Sympathetic stimulation releases norepinephrine and initiates a cyclic AMP 2nd-messenger systemFigure 18.22
46Effects of Hormones on Contractility Epi, NE, and Thyroxine all have positive ionotropic effects and thus contractilityDigitalis elevates intracellular Ca++ concentrations by interfering with its removal from sarcoplasm of cardiac cellsBeta-blockers (propanolol, timolol) block beta-receptors and prevent sympathetic stimulation of heart (neg. chronotropic effect)
47Autonomic Control of Cardiac Output Sympathetic increases cardiac outputCan increase heart rate 70 to BPM Can double force of contractionSympathetic nerves release norepinephrineBelieved to increase permeability of Ca2+ and Na+.Parasympathetic (vagal) decreases cardiacoutputCan decrease heart rate to BPMCan decrease force of contraction by 20-30%Parasympathetic nerves release acetylcholine Increases permeability to K+
48Cardiac Output and Peripheral Resistance Increasing the peripheral resistance decreases cardiac output.arterial pressure total peripheral resistancecardiac output =