Cardiac 2 Flashcards
If a question doesn’t specify which chamber it is referring to, assume ___
Left ventricle
Key terms
- Systole - ejection
- Diastole - filling
- End diastolic volume
- End systolic volume
- Stroke volume = EDV-ESV
- Ejection fraction = SV/EDV (SV is stroke volume)
- Isovolumetric contraction
- Isovolumetric relaxation
Equation for stroke volume
End diastolic volume - end systolic volume
Equation for ejection fraction
stroke volume/end diastolic volume
(High in a healthy heart)
What is isovolumetric contraction?
- A period of time when both valves to the ventricle are closed but the ventricle is squeezing
- Between the closing of the left AV valve and the opening of the aortic valve that’s isovolumetric (both valves are closed so the volume can’t change)
- This changes when the pressure in the ventricle gets higher than the residual pressure left in the aorta from the last hearbeat
What is isovolumetric relaxation?
- A period of time during relaxation (diastole) when both valves are closed
- Ends when the pressure in the ventricle drops low enough and the AV valve opens and the ventricle refills with blood
Wiggers diagram- volume
- Left ventricular volume shows that only a little bit of blood moves in when the atria contract
- Period of isovolumetric contraction
- Most of the blood is ejected in the first third of the ejection phase. This matters when the heartbeat gets faster - a lot of blood still goes out
- Ventricle relaxes, aortic valve closes, period of isovolumetric relaxation, AV valve opens and vantricle fills
- Most of the filling happens in the first third- also important when heart rate increases
- There is a plateau in blood volume before the atria squeeze
Wiggers diagram- pressure
- Has to reach down to very low pressures to fill up and has to generate maximum pressure to push blood out, so the lowest and highest pressures in the whole system are seen in the ventricle
- At the very beginning, the pressure in the ventricle is lower than the pressure in the atrium, so the AV valve is open and the ventricle is filling
- The atria contract, and then the ventricles do
- The pressure in the left ventricle exceeds the pressure in the left atrium (AV valve closes)
- Anytime pressure lines cross, a valve is changing its open or closed state!
- Pressure in the ventricle rises, but both valves are closed (isovolumetric contraction). When the pressure in the ventricle exceeds the pressure in the aorta, the aortic valve opens, and pressure peaks
- Ventricle starts to relax, pressure drops below pressure in aorta, aortic valve closes, isovolumetric relaxation, pressure in the ventricles drops below the pressure in the atria, AV valve opens, and filling begins again
If the pressure in the ventricle is lower than the pressure in the atrium, what will the movement of blood be?
The AV valve is open and the ventricle is filling
Addition of ventricular cell membrane potential to Wiggers diagram
- Depolarizes during QRS
- Repolarizes during the T-wave
Addition of ventricular cell membrane potential to Wiggers diagram
- Depolarizes during the P-wave
- Repolarizes during the QRS
Closer-up view of pressure and volume changes in the heart
- Meeting of lines at the bottom, where blue and pink meet, have to do with AV valve
- Meeting of pink and purple lines has to do with aortic valve
- Watch lecture at 45 mins for clarification
Frank-Starling Mechanism
-When more blood enters the heart, the cardiac myocytes are stretched, which causes them to generate more force
-Stretching the cardiac myocytes results in immediately more cross-bridges through two mechanisms:
- Stretch-sensitive calcium channels (if you stretch the muscle cell, more calcium gets released
AND/OR
- Stretch sensitivity of troponin- goes into a conformation that has a higher affinity to bind calcium
-Not adding more or less epinephrine to the heart - only looking at effect of end diastolic volume on stroke volume
What is end diastolic volume proportional to?
Stretch of the muscles surrounding the ventricle
What is stroke volume proportional to?
Number of cross-bridges –> tension
Overview of effect of increased stroke volume
- Stroke volume is proportional to number of cross-bridges
- More cross-bridges, more force, more stroke volume
- By stretching, maybe more calcium released or more sensitivity of troponin to calcium
Valsalva maneuver
- When you increase pressure in the thoracic cavity, you start to cut off blood flow returning to the heart
- Frank-Starling is the most important concept in explaining why blood pressure in the carotid arteries drops during this maneuver and heart rate picks up as compensation
- It’s analogous to clipping off the superior and inferior vena cava, starving the heart of blood (venous return)
- If you don’t have enough blood to fill the ventricle, the ventricles’ end diastolic volume decreases, so the stroke volume is smaller –> less cardiac output into aorta –> lower blood pressure in carotid artery in neck
What changes in the body happen during the Valsalva maneuver?
- Kicks in sympathetic nervous system to get heart rate beating faster (can measure with EKG)
- Heart also tries to squeeze with more force
- Blood vessels increase peripheral resistance to keep pressure high
- When you release the strain phase, you get a bolus of blood rushing into the heart that’s beating faster and stronger against a blood vessel system that has a higher resistance and veins that are squeezing to get more blood back to the heart, causing spike in blood pressure
- Heart rate slows down
What is contractility controlled by?
Factors outside of the heart- nervous innervation primarily
Contractility graph
- Under sympathetic stimulation, for the same end diastolic volume, you’ll get a bigger stroke volume
- This has to do with the effect of norepinephrine, which binds to adrenergic receptors and causes more calcium to be released through a separate mechanism than the ones involved in Frank-Starling
Can the length-tension relationship explain Frank-Starling?
- No
- Old story: In low ventricular volume scenarios, the sarcomeres are in a less optimal overlay, in which they interfere with each other, yielding fewer cross-bridges. Stretching the heart gives you a more optimal overlay of actin and myosin and results in more cross-bridges.
- This is wrong. The heart beats at a low volume most of the time (when you’re not exercising). This would mean that most of the time, you would have a very inefficient overlay of actin and myosin.
Explanation of length-tension graph for skeletal muscle
- The blue line is the length-tension relationship in the skeletal muscle
- Ideal length of sarcomere is 2-2.2. The plateau is when you get the maximal number of cross-bridges, based on the arrangement of thick and thin filaments
- When you start stretching the muscle out to longer lengths, the tension decreases, as it does when the sarcomere is too short.
- The green line is the passive skeletal muscle line. As you start stretching the muscle, at a certain point, you’ll stretch it to its limit, and you’ll have tension even when the muscle’s not contracting.
Explanation of length-tension graph for cardiac muscle
- These two curves for skeletal muscle are very different from cardiac muscle.
- The active cardiac curve shows that when the sarcomeres are within 1.9 and 2.2 micrometers, which corresponds to the plateau in skeletal muscle where things are optimal, small changes in length in cardiac muscle give you big changes in tension/force.
- So the overlay of actin and myosin is optimal throughout all of the lengths realized during normal cardiac volumes.
- So there’s an interference- something else is prohibiting sarcomere length 2.0 giving you maximum tension. What’s inhibiting it is not as much calcium is being released as could be and troponin isn’t as sensitive to calcium as it could be (not exposing enough binding sites)
- By having a little bit of stretch, e.g. from 1.9 to 2, you still have optimal overlay of actin and myosin, but you’re getting more calcium and better troponin activity to give you more cross-bridges. That’s the Frank-Starling mechanism.
- All the way through the sarcomere lengths of 1.9 to 2.2, more stretch gives you more tension.
- If you go too far, stretch beyond 2.4, tension goes down steeply. Frank-Starling would fail you here because even if you’re releasing more calcium, even though troponin’s very sensitive, you’re pulling the sarcomeres so far apart that you don’t have enough cross-bridges. This is one of the most dangerous parts of chronic heart failure.
- So there’s some other mechanism (other than Frank-Starling) that’s giving you a very steep slope in the relationship between sarcomere length and tension, where small changes in sarcomere length that don’t impact optimal overlay are giving you big changes in tension.
What happens if heart muscle gets stretched too much?
- If you go too far, stretch beyond 2.4, tension goes down steeply. Frank-Starling would fail you here because even if you’re releasing more calcium, even though troponin’s very sensitive, you’re pulling the sarcomeres so far apart that you don’t have enough cross-bridges.
- This is one of the most dangerous parts of chronic heart failure.
Frank-Starling Effect
- Over the sarcomere length where Frank Starling is observed, the overlay of actin and myosin is always optimal. Therefore stretch must yield more crossbridges.
- Putative mechanism 1 - there is a stretch-sensitivity to calcium channels in membrane or SR that result in increased [Ca++] inside with increased stretch
- Putative mechanism 2 - there is a stretch-sensitive change in troponin/tropomyosin such that affinity for Ca++ increases with increased stretch
Summary of Frank-Starling from textbook
- The normal point for cardiac muscle in a resting individual is not at its optimal length for contraction, as it is for most resting skeletal muscles, but is on the rising phase of the curve.
- For this reason, greater filling causes additional stretching of the cardiac muscle fibers and increases the force of contraction.
- The mechanisms linking changes in muscle length to changes in muscle force are more complex in cardiac muscle than in skeletal muscle.
- In addition to changing the overlap of thick and thin filaments, stretching cardiac muscle cells toward their optimum length decreases the spacing between thick and thin filaments (allowing more cross-bridges to bind during a twitch), increases the sensitivity of troponin for binding Ca2+, and increases Ca2+ release from the sarcoplasmic reticulum.
Impact of sympathetic stimulation on calcium release and force
- Along with Frank-Starling, increased sympathetic stimulation causes increased calcium in and increased force, as well as faster force generation
- Force develops more quickly and peaks at a higher value (more cross-bridges)
- Faster force generation due to faster release of calcium
- Force also dissipated more quickly because calcium pumped back into SR faster.
- So there’s a shorter depolarization, but the spike in calcium is greater, giving you a heartbeat that is stronger and faster
Pressure vs. volume loop (connection with Wiggers diagram)
- X-axis: left ventricular volume
- Y-axis: left ventricular pressure
- As the volume increases during diastole, the pressure stays the same, until the end when the ventricle goes into systole, and the AV valve closes, the volume no longer increases and the pressure rises
- It rises from EDV to C (isovolumetric contraction) and when the pressure in the ventricle exceeds the pressure in the aorta, the aortic valve opens at C
- At C, the blood is ejected, and then decreases to D
- After D, there is isovolumetric relaxation until A, when the pressure in the ventricle drops below the pressure in the atria and the AV valve opens, causing filling of the ventricle
- At every letter (A, B, C, D), a valve changes state
How to find stroke volume from pressure volume loop
Diameter of loop (difference between volume at B and at A)
How can the work that a ventricle is doing on one heartbeat be quantified?
- How much volume it’s pushing out + against how much pressure/how much pressure it’s taking to do that
- Area under the curve is a measure of how much work is being done
Pressure volume changes (watch lecture at 1:09)
Increased EDV- watch lecture at 1:18)
Pressure curve
Increased afterload on pressure curve
-
Decreased contractility on pressure curve
What is the equation for cardiac output?
Cardiac output = heart rate x stroke volume
What is heart rate determined by?
The heart and degree of sympathetic/parasympathetic input.
What is stroke volume determined by?
A number of factors; some related to heart function (i.e. contractility) and most related to the state of the vascular system.
What are preload and afterload determined by?
Blood vessels
Flow chart showing physiological factors that affect cardiac output
What factors can increase cardiac output (flow chart)
- Increased cardiac output can be caused by increased heart rate (SA node), which is determined by sympathetic and parasympathetic.
- Decreased parasympathetic increases heart rate.
- Increased sympathetic also increases HR. Sympathetic also has hormones in the blood, so plasma and epinephrine can also impact heart rate.
- The second factor is stroke volume. It is impacted by the effects of epinephrine on blood vessels.
- Sympathetic activity also increases stroke volume by increasing contractility.
- End diastolic ventricular volume (preload) is determined by blood vessels and increases stroke volume.
- The first two factors (epinephrine and sympathetic) have to do with the heart, whereas preload has to do with changes in blood vessels.
What would happen if all you did was stimulate the heart to beat faster and stronger but not change the state of the blood vessels?
- Cardiac output would only go up slightly (5-6 liters/minute)
- In order to get up to 25 liters/minute, you have to activate the heart and change the state of the blood vessels
- Otherwise, the blood would run out of blood to pump if the blood is just trickling back to the heart instead of being coaxed back to the heart
