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Part 1:
*Defining ventricular preload*
The conceptual definition of preload is quite straightforward: end-diastolic myocardial load/stretch. At the microscopic level, it& #39;s the sarcomere length we are interested in, which would increase with higher end-diastolic load (preload)
1/
*Defining ventricular preload*
The conceptual definition of preload is quite straightforward: end-diastolic myocardial load/stretch. At the microscopic level, it& #39;s the sarcomere length we are interested in, which would increase with higher end-diastolic load (preload)
1/
2/
The importance of preload is in effecting the Frank-Starling mechanism: increase in ventricular performance with
https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben"> preload. The basis of F-S relationship is primarily the sarcomere Force-Length relation.
At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized.
The importance of preload is in effecting the Frank-Starling mechanism: increase in ventricular performance with
At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized.
preload. The basis of F-S relationship is primarily the sarcomere Force-Length relation.At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized." title="2/The importance of preload is in effecting the Frank-Starling mechanism: increase in ventricular performance with https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben"> preload. The basis of F-S relationship is primarily the sarcomere Force-Length relation.At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized.">
preload. The basis of F-S relationship is primarily the sarcomere Force-Length relation.At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized." title="2/The importance of preload is in effecting the Frank-Starling mechanism: increase in ventricular performance with https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben"> preload. The basis of F-S relationship is primarily the sarcomere Force-Length relation.At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized.">
3/
Any further increase in sarcomere length does not improve ventricular performance (flat part of F-S curve).
So when we give fluids, what we& #39;re really trying to achieve is anhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">in the average sarcomere length.
~~~
The clinical definition of preload is much more controversial!
Any further increase in sarcomere length does not improve ventricular performance (flat part of F-S curve).
So when we give fluids, what we& #39;re really trying to achieve is an
~~~
The clinical definition of preload is much more controversial!
4/
For LV, the two most commonly used measures are LVEDV and LVEDP
Before we compare these, let& #39;s model the ventricle as a fluid-filled perfectly spherical balloon (obviously an approximation). If we fill the balloon with more fluid, it& #39;s size (LVEDV) and pressure (LVEDP) willhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">
For LV, the two most commonly used measures are LVEDV and LVEDP
Before we compare these, let& #39;s model the ventricle as a fluid-filled perfectly spherical balloon (obviously an approximation). If we fill the balloon with more fluid, it& #39;s size (LVEDV) and pressure (LVEDP) will
5/
*Core point*
To have any load/stretch on the wall of the balloon, it needs to be filled beyond its "unstressed volume". E.g. if the balloon is not filled enough to cause a stress on its walls (all volume = unstressed volume; no stressed volume), the "load" on its wall is zero!
*Core point*
To have any load/stretch on the wall of the balloon, it needs to be filled beyond its "unstressed volume". E.g. if the balloon is not filled enough to cause a stress on its walls (all volume = unstressed volume; no stressed volume), the "load" on its wall is zero!
6/
**Pitfalls with LVEDV**
(i) For a given LVEDV, the wall stretch (and LVEDP) would vary depending on the physical characteristics of the ventricle. E.g. 110cc is a normal adult LVEDV but would generate enormous LVEDP in kids!
Another example is eccentric hypertrophy (in DCM).
**Pitfalls with LVEDV**
(i) For a given LVEDV, the wall stretch (and LVEDP) would vary depending on the physical characteristics of the ventricle. E.g. 110cc is a normal adult LVEDV but would generate enormous LVEDP in kids!
Another example is eccentric hypertrophy (in DCM).
7/ As new sarcomeres are added in series, the unstressed volume of LV https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">. So the same LVEDV would generate https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">LVEDP compared to normal hearts.
(ii) Secondly, LVEDV disregards unstressed volume. E.g. in our model, balloon A has some volume (LVEDV) but its pressure (LVEDP) is zero!
(ii) Secondly, LVEDV disregards unstressed volume. E.g. in our model, balloon A has some volume (LVEDV) but its pressure (LVEDP) is zero!
. So the same LVEDV would generate https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">LVEDP compared to normal hearts.(ii) Secondly, LVEDV disregards unstressed volume. E.g. in our model, balloon A has some volume (LVEDV) but its pressure (LVEDP) is zero!" title="7/ As new sarcomeres are added in series, the unstressed volume of LV https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">. So the same LVEDV would generate https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">LVEDP compared to normal hearts.(ii) Secondly, LVEDV disregards unstressed volume. E.g. in our model, balloon A has some volume (LVEDV) but its pressure (LVEDP) is zero!" class="img-responsive" style="max-width:100%;"/>
8/
**Pitfalls of LVEDP**
In my mind, LVEDP is a much more robust measure of LV preload and circumvents the pitfalls of LVEDV. However, a few considerations:
(i) It& #39;s the *transmural* LVEDP that matters (more on this later)
(ii) A given LVEDP doesn& #39;t fully describe wall stress
**Pitfalls of LVEDP**
In my mind, LVEDP is a much more robust measure of LV preload and circumvents the pitfalls of LVEDV. However, a few considerations:
(i) It& #39;s the *transmural* LVEDP that matters (more on this later)
(ii) A given LVEDP doesn& #39;t fully describe wall stress
9/ Why? Enter LaPlace& #39;s law! {T=PR/2w}
For a given LVEDP, the amount of wall tension is dependent on the curvature of the sphere. If curvature is low (bigger sphere), same pressure causes higher wall tension.
Here& #39;s an excellent tweetorial on this - https://twitter.com/AndrewCAhn2/status/1129510075259793413">https://twitter.com/AndrewCAh...
For a given LVEDP, the amount of wall tension is dependent on the curvature of the sphere. If curvature is low (bigger sphere), same pressure causes higher wall tension.
Here& #39;s an excellent tweetorial on this - https://twitter.com/AndrewCAhn2/status/1129510075259793413">https://twitter.com/AndrewCAh...
10/ *Wall stress/tension* provides the complete description of ventricular preload. Wall tension is the orthogonal stress on the LV wall that would be proportional to average sarcomere length.
LaPlace& #39;s law states that:
Tension (T) = (Pressure x radius) / 2.width (LV thickness)
LaPlace& #39;s law states that:
Tension (T) = (Pressure x radius) / 2.width (LV thickness)
11/
Summary:
For a *stressed LV*, preload is a function of LVEDP, LVEDV and LV thickness (w)
Mathematically, volume is the cube root of radius, so the influence of LVEDP > LVEDV.
Also, a thick LV (https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">w) (e.g. HTN), would result in a lower wall stress for a given LVEDP/LVEDV.
Summary:
For a *stressed LV*, preload is a function of LVEDP, LVEDV and LV thickness (w)
Mathematically, volume is the cube root of radius, so the influence of LVEDP > LVEDV.
Also, a thick LV (
12/ **Special scenario: RV**
Here& #39;s the kicker with RV preload: normal human RV operates at or below its unstressed volume! (PMID: 27613549).
Volume loading a normal RV initially does not invoke the F-S mechanism as its wall stress (preload) is zero! (RVEDV < unstressed volume)
Here& #39;s the kicker with RV preload: normal human RV operates at or below its unstressed volume! (PMID: 27613549).
Volume loading a normal RV initially does not invoke the F-S mechanism as its wall stress (preload) is zero! (RVEDV < unstressed volume)
13/ Of course, a volume overloaded RV would operate via the F-S curve.
This under-appreciated fact has critical implications:
(i) (Transmural) RA pressure is normally zero.
(ii) Hence, in an unstressed RV, a CVP reading > zero reflects pericardial pressure (more on this later).
This under-appreciated fact has critical implications:
(i) (Transmural) RA pressure is normally zero.
(ii) Hence, in an unstressed RV, a CVP reading > zero reflects pericardial pressure (more on this later).
Here& #39;s a beautiful commentary unifying wall stress to explain both preload and afterload: PMID: 11824209
Submitting for peer-review with the Heart Failure community!
@FH_Verbrugge @VerwerftJan @TheWrightHeart @CharlieJainMD @yreddyhf @RyanTedfordMD @OKiamanesh @SunitChaudhryMD
Submitting for peer-review with the Heart Failure community!
@FH_Verbrugge @VerwerftJan @TheWrightHeart @CharlieJainMD @yreddyhf @RyanTedfordMD @OKiamanesh @SunitChaudhryMD
