Cardiology:: Cardiac Output Module

What variables determine stroke volume?

Stroke volume is a function of preload, afterload, and contractility. Preload is directly proportional to stroke volume Afterload is inversely proportional to stroke volume Contractility is directly proportional to stroke volume

How is central venous pressure increased/decreased?

Sympathetic activity increases tension in walls of veins (and arteries). This increases central venous pressure and pushes blood into the right atrium, increasing preload. The majority of our blood is in the veins/veinules. Increased blood volume would lead to increased preload. Body position changes central venous pressure. If we're standing, gravity causes decrease in central venous pressure. If we're lying down, gravity evenly hits CVP throughout body and doesn't cause an impact. Increased arteriolar dilation leads to increased CVP.

What factors influence afterload?

Systemic Vascular Resistance Ventricular Pressure Aortic pressure Aortic compliance Aortic Valve resistance

How do calcium channel blockers impact heart rate?

Calcium channel blockers decrease heart rate.

How do nitrates impact vascular tone?

*Nitrates decrease vascular tone*. Nitrates cause vasodilation (primarily venodilation), by acting like nitric oxide (NO), the predominant endothelial-derived vasodilator.

How do beta blockers impact afterload?

*beta blockers do not impact afterload*

How do calcium channel blockers impact preload?

*calcium channel blockers do not impact preload*

What is afterload?

Afterload is the pressure within the arteries that the ventricles must overcome before pushing blood through the aortic valve. Increased afterload decreases stroke volume. Afterload is defined as wall stress (LaPlace's law) Afterload = Pressure * radius / (2*thickness) Afterload is a function of ventricular pressure. Afterload is often approximated as aortic pressure. Afterload can be represented as LV systolic pressure in the PV loop.

What is the cardiac performance curve?

Also called the Frank-Starling Curve The cardiac performance curve describes how stroke volume increases with increased left ventricular end diastolic volume. The Frank-Starling Curve is an empirically derived argument supporting the idea that the entire heart behaves the same way a single sarcomere behaves when exposed to increased tension. More pressure/tension/wall tension on the wall of a ventricle leads to increased force generation. More force generation means larger stroke volume. How do you get increased LVEDP? Increase LVEDV

What's going on in this patient? Blue is normal, red is new

Answer below Increased contractility. You can see the stroke volume has increased, because the end diastolic volume has decreased. The ventricle is able to push more blood out of the heart and into the aorta.

What physiologic change has happened in this patient? Red is new, blue is original system.

Answer below: Decreased stroke volume Increased end diastolic volume Constant end systolic volume This is increased afterload

What variable changed in this patient's cardiac cycle? (blue is normal, red is changed) Describe what's going on in each of the lettered portions of the PV loop.

Answer below: Increased preload A = ventricular filling B = isovolumic contraction C = arterial filling D = isovolumic relaxation

Explain each of these points

Answers below: a) Opening of aortic valve b) End of atrial systole (closing of mitral valve) c) Closing of aortic valve d) opening of mitral valve e) increase in atrial pressure secondary to ventricular contraction

How do beta blockers impact contractility?

Beta blockers actively decrease contractility by decreasing calcium channel activity in cardiac myocytes. This decreases speed of contraction and strength of contraction (less calcium in the cell = less sarcomere activity). *beta blockers actively decrease contractility*

How do beta blockers impact preload?

Beta blockers can cause a bit of vasoconstriction (b2 is a vasodilator), but these effects are marginal and do not impact preload. *beta blockers do not impact preload*

How do beta blockers impact heart rate?

Beta blockers directly decrease heart rate by inhibiting sympathetic innervation of the SA and AV nodes. Beta blockers decrease L-type and T-type calcium channel activity, and HCN channel activity. This decreases automatic depolarization of nodal cells and slows heart rate. *beta blockers decrease heart rate*

How do beta blockers impact coronary blood flow?

Beta blockers do not impact coronary artery flow.

How do beta blockers impact vascular tone?

Beta blockers marginally increase vascular tone. Remember that beta2 receptors cause vasodilation. So blocking beta2 can cause marginal vasoconstriction. *but beta blockers do not appreciably impact coronary blood flow, afterload, or preload*

Does preload refer to pressure or volume?

Both! Preload is most closely defined as wall tension in the ventricle prior to contraction. This is LaPlace's law. Wall tension = P*r/(2*h). Increased pressure (from fluid pushing into a confined space) would increase P. Increased volume (ventricle expanding a bit because of compliance while fluid flows in) would increase r. Both of these increase wall tension, which is equated to an increase in preload.

How do calcium channel blockers impact contractility?

Calcium channel blockers actively decrease contractility. Decreased intracellular calcium = decreased contraction.

How do calcium channel blockers impact vascular tone?

Calcium channel blockers cause vasodilation. They decrease vascular tone.

How do calcium channel blockers impact coronary blood flow?

Calcium channel blockers cause vasodilation. This increases the ability of the coronary arteries to feed the heart. Calcium channel blockers increase coronary artery blood flow.

How does contractility show up in a pressure volume loop?

Contractility affects the active pressure-volume curve. Increased contractility increases maximum pressure generated by the heart. But the aortic pressure hasn't changed, so the pressure at which the aortic valve opens does not change. But! The total tension generated increases, so the end systolic volume decreases. You have a stretching of the PV loop to the left, without a shift in the right-most points.

How would you define contractility?

Contractility is an intrinsic property of cardiac myocytes to generate force. Physiologically, it is a function of Ca2+ L-type channels, ryanodine receptors, and SERCA activity. Contractility determines the baseline strength of a contraction. It is not impacted by pressure/volume/preload/afterload (although these do change a heart's position on the length-tension/frank-starling curve)

What is the relationship between contractility and preload or afterload?

Contractility is an intrinsic property, unchanged by preload, afterload, filling volume, ventricular pressure. Contractility soleyl represents the amount of and speed with which calcium ions are dumped into the cell, to bind with troponin and free up myosin for cross-bridging with actin.

What is contractility?

Contractility is the contractile force developed by the ventricle at any given preload/afterload. Contractility is how much Ca2+ is being released with each beat of the heart. Increased Ca2+ release leads to increased actin-myosin cross-bridging Increased contractility --> increased stroke volume.

What impact would venodilation have on preload?

Decrease preload (less of a pressure gradient pushing blood back into heart)

How does aortic compliance impact afterload?

Decreased compliance increases afterload. The vessel walls do not "give" as much during systole, which increases systemic vascular resistance and gives the ventricle more to push against.

What variables determine cardiac output?

Heart Rate and Stroke Volume Heart Rate is influenced by sympathetic/parasympathetic nervous activity. Stroke volume is influenced by metabolic vasodilation of coronary arteries (heart needs blood to work), Stroke volume is mostly impacted by preload, afterload, and contractility. Preload is directly proportional to stroke volume. Afterload is inversely proportional to stroke volume. Contractility is directly proportional to stroke volume.

Explain this graph

Heart rate increases from 40-90 bpm do not increase cardiac output as much as expected because you decrease preload as your heart rate increases. The decreased preload counters some of the increased heart rate. 90-170 is proportional/expected linear relationship >170 actually decreases cardiac output because you have less filling time (less diastole)

Explain each of these graphs

Heart sounds: S1 is mitral valve and tricuspid valve shutting (pressure in ventricle rises past pressure in atria). S2 is aortic and pulmonic valve shutting (aortic pressure rises above ventricular pressure) LV volume/time: LV volume rises during diastole. During systole there is isovolumic contraction and then a decrease in volume as blood is pushed into the aorta. Isovolumic relaxation, and then filling begins again. Atrial pressure/time: contraction leads to a slight increase. Relaxation leads to dip, but ventricular contraction causes a secondary rise. Atrial filling leads to slow rise, but ventricular relaxation leads to secondary dip. Aortic pressure/time: Aorta is high pressure system (closed off from ventricle) slowly losing pressure as it pushes blood through the body. Aortic pressure drops as LV pressure rises until they equal and aortic valve opens. During open systole the pressures of both systems are comparable. As LV pressure drops, the aortic valve shuts and the cycle repeats. LV pressure/time: Slight increase in pressure during filling and atrial contraction. Massive increase during ventricular contraction. Decrease during relaxation.

What is the relationship between left ventricular end diastolic volume and maximum systolic pressure?

Higher pressures are achieved in contraction when there's a "more full" ventricle. This makes sense, because you have more fluid, so even with the same contraction force you get increased pressure. But it's not the same contraction force! You have increased stretching of the myocytes which increases tension (length-tension curve) The passive pressure/volume curve is very slightly sloped. This could be because the walls of the ventricle comply with increasing fluid, stretching out to increase total chamber volume a bit.

What are common causes of increased afterload?

Hypertension Arteriosclerosis Aortic stenosis

What impacts contractility?

If you exercise a bunch, you can increase your heart's contractility. Sympathetic nervous system activity can increase contractility.

What is the Frank-Starling Mechanism?

If you take an individual sarcomere and increase its length (to a point), you increase the force generated by the muscle. The Frank-Starling Mechanism is the argument that the length-tension curve can be used to describe individual muscles, and individual muscles can be used to describe the heart.

What impact would venoconstriction have on preload?

Increase preload (more of a pressure gradient pushing blood back into the heart)

What is the relationship between preload and stroke volume?

Increase preload and you'll increase stroke volume.

What is the relationship between afterload and blood pressure?

Increased MAP = increased afterload

What is the cellular explanation for the effects of afterload on stroke volume?

Increased afterload means the muscles of the heart have to work harder to constrict. It takes them longer to decrease their length, which means ventricular contraction is lengthened. But the myocytes had a set amount of work they could do. This means by the time the aortic valve is open, the myocytes are almost exhausted and finish their contraction. The valve soon shuts, before much blood was pushed out. Increased afterload decreases stroke volume, because *it takes longer during systole for the ventricular pressure to reach the aortic pressure*

How does an increased afterload show up in a PV loop?

Increased afterload will decrease your end systolic volume and increase your end systolic pressure without changing any of the end diastolic volume/pressure values.

What is the relationship between contractility and stroke volume?

Increased contractility = increased stroke volume at a given LVEDV/LVEDP

What is the relationship between contractility and slope of the ventricular systolic pressure curve?

Increased contractility = steeper slope of the ventricular systolic pressure curve (the ventricle is able to contract quicker and more strongly)

What is the relationship between contractility and the end systolic pressure volume relationship?

Increased contractility will increase the slope of and raise the end systolic pressure volume relationship curve. This means that you can squeeze more fluid out of the heart before the atrial valve shuts.

How does preload impact stroke volume?

Length-tension curve is critical in understanding this concept. There is a certain myocyte length (a given amount of stretch) that is associated with maximal tension during contraction (assuming that length stays constant throughout contraction). Increased preload leads to a more full, pushed-out ventricular chamber. The myocytes are at a more optimal spot of the length-tension curve and are able to produce more tension when they contract. Increased tension leads to increased pressure which leads to increased stroke volume.

What does increased preload do to the PV loop?

Increased preload will stretch the PV loop to the right without shifting the end systolic volume, increasing the stroke volume.

What is the relationship between systemic vascular resistance and afterload?

Increased systemic vascular resistance = increased afterload.

What is the relationship between valvular stiffness and afterload?

Increased valvular stiffness = increased afterload (valve is adding resistance to flow out of ventricle)

What is the relationship between calcium availability and contractility?

Intracellular calcium levels determine the strength of a sarcomere response. Increased calcium levels allow for more sarcomeres to become active, increasing the total force generated by the cardiac muscle. Calcium channels, the ryanodine receptors, and SERCA all play a role in adjusting contractility.

What factors determine contractility?

Intracellular calcium levels! SR release of Ca2+ Influx of Ca2+ (increase with SNS, decrease with amlodipine) Removal of Ca2+ myosin ATP-ase (increased by extensive, rigorous training) ATP levels (ichemia. hypoxia) Number of sarcomeres

How do nitrates impact preload?

Nitrates cause massive venodilation. Venodilation leads to decreased filling of the right atrium, which decreases preload. *nitrates drastically decrease preload*

How do nitrates impact afterload?

Nitrates cause some arteriodilation (predominately venodilation), which decreases pressure in the arteries. This decreases the force that ventricles have to push against when ejecting fluid (which is afterload). *nitrates decrease afterload*

How do nitrates impact heart rate?

Nitrates cause vasodilation (predominately venodilation), which decreases preload. This decreases oxygen demands of the heart. Coronary artery dilation also provides more oxygen to the heart. Arteriodilation leads to decreased afterload. So the heart doesn't have to push as hard to get a given amount of blood into the aorta. Stroke volume is net decreased (preload decreases more than afterload decreases). We want to keep CO constant, so heart rate has to increase to compensate. *nitrates mildly increase heart rate*

How do nitrates impact contractility?

Nitrates do not impact contractility. Nitrates act like Nitric Oxide, purely causing vasodilation in different blood vessels. Contractility is an intrinsic property of cardiac myocytes, unaffected by pressures or volumes of blood in the heart. *nitrates do not impact contractility*

How do nitrates impact coronary blood flow?

Nitrates moderately increase coronary blood flow by causing coronary artery vasodilation. Nitrates act like nitric oxide, decreasing contraction of smooth muscle cells in the walls of blood vessels. Nitrates increase cGMP concentrations in the body. cGMP activates myosin light chain phosphatase. MLCP causes dissociation of phosphates from myosin, which stops contraction.

What impact would phenylephrine have on contractility?

None! Phenylephrine is an alpha 1 agonist. It would cause vasoconstriction, which increases both preload and afterload. But contractility is not a function of preload or afterload.

What impact would phenylephrine have on stroke volume?

Phenylephrine is an alpha 1 agonist. Phenylephrine causes vasoconstriction, increasing afterload AND preload. BUT! Phenylephrine preferentially acts on the veins, increasing venoconstriction more than arterioconstriction. This means phenylephrine increases preload more than it increases afterload. The net effect is to increase stroke volume.

What point on the PV loop refers to preload?

Point B! This is the highest pressure/volume point before ventricular contraction Remember that preload is a function of end diastolic pressure AND volume

What is preload?

Preload is the amount of passive tension or passive stretch on the ventricular myocardial cells just prior to ventricular contraction. Preload is the fluid load of blood in the ventricle's chamber before contraction. Increased LVEDV increases pre-load.

Where do you find preload in the PV Loop graph?

Preload is the pressure at the maximum volume in the passive component of the PV Loop.

What are the major determinants of aterload?

Systemic vascular resistance (mainly arterial/arteriolar resistance) is a determinant of afterload for the LEFT VENTRICLE. Pulmonary vascular resistance is a determinant of afterload for the RIGHT VENTRICLE. Aortic compliance (normally quite compliant) Aortic valve resistance (normally negligible)

What is the relationship between LaPlace's law and preload?

Preload ~= wall tension in right ventricle before systole ~= P*r/(2*h). Increased filling = increased pressure and increased radius = increased wall tension. Increased wall tension = increased contraction strength.

What is the relationship between preload and cardiac myocyte force generation?

Preload ~= wall tension in the ventricles during diastole. wall tension is related to muscle force-generation via the length-tension curve. Increased length = increased tension the muscle can generate. This approximation is called the Frank-Starling Mechanism So increased preload leads to increased tension during contraction for a given muscle. Preload is a function of ventricular pressure and volume immediately before systole.

How do you approximate systemic vascular resistance?

Systolic blood pressure is a reasonable proxy for systemic vascular resistance. P=Q*R If we know Q (stroke volume * heart rate), and we know P (systolic blood pressure), R (systemic vascular resistance) is known. Systemic vascular resistance is a proxy for afterload (what the heart has to push against) for the left ventricle.

How do you define afterload?

Tension on the ventricular wall *during systole*, the pressure the ventricle has to fight to eject blood into systemic circulation. Afterload = wall stress ~= Pressure * radius / (2*wall thickness)

Why don't we see the heart reaching its maximum achievable pressure during systole?

The aortic valves open during systole (once the ventricular pressure equals the arterial pressure). Blood begins to leave the ventricle, so you no longer have the same closed system. You won't reach maximum isovolumic pressure because the system gains volume.

What factors determine preload?

The main factor is central venous pressure. Central venous pressure is the hydrostatic pressure in the large veins of systemic circulation. Central venous pressure = right atrium pressure (there's no valve between these systems) Increased pressure in right atrium pressure leads to increased filling of the ventricles = increased preload. Since there's conservation of mass between right heart and left heart, there's increased blood flow through pulmonary circulation and increased filling of left ventricle. *any change in CVP, pulmonary, or atrial pressures will change preload*

What is the Frank-Starling Law of the Heart?

The ventricles will pump out as much blood as is put in them. If more blood fills the heart during diastole, more blood will be pumped out during systole. Increasing end diastolic volume or end diastolic pressure will lead to increased stroke volume.

What is filling pressure?

This is a clinician's term for preload. It represents the tension felt by the walls of the ventricle at the end of diastole.

What is the end diastolic pressure volume relationship?

This is an empirical approximation of the relationship between pressure and volume in a relaxed ventricle. As the ventricle fills, there will be an increased volume without any change in pressure. Once the ventricle is full, fluid (being incompressible) doesn't have anywhere to go. As fluid pushes into the ventricle, the walls stretch a bit, but pressure begins to rise more rapidly. Both the pressure and the stretching of the ventricle impact the wall tension in the ventricle and impact the ability of the heart to generate force. (more wall tension = more force generation)

What is the end systolic pressure volume relationship?

This is an empirical approximation of the strength of cardiac myocyte contraction at a given volume. Increased end diastolic volume increases preload which then allows the myocytes to contract more strongly. This increases the maximum systolic pressure reached. So as you increase volume, you increase pressure. (think of LaPlace's law)

What is the relationship between left ventricular end diastolic volume and stroke volume?

This is what we analyze in cardiac performance curves. Left ventricular end diastolic volume is directly related to stroke volume. Increased LVEDV leads to increased systolic pressure which ends up pushing more fluid out of the heart (increasing the stroke volume)

Where do you find afterload in the PV loop?

Unlike preload, afterload cannot be defined by a single point. Instead, afterload can be visualized as the upper bound of the PV loop. It is a series of points (because afterload is wall tension *throughout* systole) showing what the ventricle has to push against.

What are major mechanisms for regulating preload?

Venodilation = decreased preload Venoconstriction = increased preload Increased blood volume = increased preload Decreased blood volume = decreased preload Laying down = increased preload (not by much) Standing up = decreased preload (not by much)

How do you measure/qualify left ventricular preload?

You can look at the external jugular vein! This is a large, visible vein in the neck. It connects directly to the superior vena cava, which connects directly to the right atria. During diastole the tricuspid valve is open, so right ventricular pressure = right atrial pressure. Left ventricular pressure can be approximated as right ventricular pressure. Obviously this is qualitative. If you want a better idea do a right or left heart catheterization.

How do calcium channel blockers impact afterload?

calcium channel blockers cause vasodilation (primarily arteriodilation). This decreases afterload. Calcium channel blockers decrease afterload.