Session_2.ppt

7/29/2019 Session_2.ppt

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CLINICAL CARDIAC MUSCLEPHYSIOLOGY

Burt B. Hamrell, M.D., Ph.D.Room 236; [email protected]


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EXCITATION-CONTRACTIONCOUPLING


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Ca2+ & Cardiac Muscle

DEPENDENCE ON EXTERNAL Ca2+

Skeletal

CardiacCa++ - INDUCEDCa++ - RELEASE!


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Small amount of Ca entering during action potential binds to ryanodinereceptors on SR, triggering release of large amount of Ca from SR

The amount entering can vary from ap to ap and is reflected in theamplitude and duration of phase 2 of the ap

The major source (~70%) of Ca for binding to troponin C is the SR

CALCIUM-

INDUCED-

CALCIUM-

RELEASE

Ca++ enters L-

Type channels

during Phase 2 of

AP, which binds

to RyR on SR,

and causes more

Ca++ to enter the

cytosol and bind

TROPONIN C!


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3 functions of Ca influxduring action potential: (during phase 2 from

ECF)

1. Direct effect on troponin C2. Ca-induced Ca release from SR3. Loading of Ca into SR (some of the entering calcium can be taken

up by the SR rather than being pumped back out of the cell)


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RelaxationA. NCX across plasma membrane (not in skeletal!)

Na-coupled countertransport (3Na+-1Ca++antiporter) (2nd active transport)

B. Active transport into SR SERCA (sarco-endoplasmic reticulum Ca-

ATPase)

Inhibited by phospholamban(NO PLBM in

SKELETAL)


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RelaxationC. The amount pumped into the sr vs. the amounttransported out of the cell can vary from beat to beat thusinfluencing the amount that can be released from the srduring subsequent beats

D. Variations in the amounts of Ca entering the cell duringan action potential and in the amounts of Ca releasedfrom the sr will influence force of contraction (more aboutthis later); however overall balance over time is

maintained. (short-term contractility changes)

Phophorylating

PLBM =

INACTIVATE

S IT!!!!!!


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At lengths >Lo, there is less overlap of

thick and thin filaments

At lengths


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ContractilityDUE TO INCREASED INTRACELLULAR CA LEVELS!!

Theability of the heart to develop force which is INDEPENDENT of

the load (preload and afterload)

does NOT depend on stretch!!

Note that contractility also is referred to as inotropic effect.

(Afterload)

contractility = force & velocity (and Vmax)


NOTE: Vmax CHANGES WITH

CONTRACTILITY!!!!


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2K+


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Tension (Force) - Length Relation


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Force-Velocity Relationand Resting Muscle Length


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Vmax

Isometric

Total

Force

fillingEDV

lengthCa affinity

for TnCforceall

velocities OTHER thanVmax (Vmax is SAME!)


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Inotropism or ContractilityUsually due to SYMPATHETIC stimulation (catecholamines)

acting on 1 receptors on myocytes!

OVERALL: Ca++ intracellularly contractility!


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Preload


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IncreasedContractility

DecreasedContractility

Control

Resting

Force


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CONTRACTILITY:

- O2 delivery

- Sympathetic activity

- Ca++ channel

blocker/ blocker

Same Preload (EDV)!!


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Effects of Contractility

Changes on the Force-Velocity Relation


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NOTE: Vmax CHANGES WITH

CONTRACTILITY!!!!


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Treppe(Staircase)


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Changes in Frequency of Contraction (exampleHR)

With an increase in frequency of contraction there is less time for Na-Ca

exchange across the cell membrane

HR = BPM = duration of AP (phase 2 plateau) = frequency of contraction

= Ca++ intracellularly = time for NCX to remove


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Normally (in vivo)an increase in HR is

due to SYMPATHETIC stimulation

meaning that CONTRACTILITY has also

increased! (HR contractility due to

sympathetic activity)


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CARDIOVASCULAR PHYSIOLOGY

Ventricular FunctionBurt B. Hamrell, M.D., Ph.D.

Room 236; [email protected]

Video, LV

Echo, is in

video folder inAngel


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Determinants of

Ventricular FunctionFilling EDV/EDP

Contractility

Afterload


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Filling/PreloadfillingEDVlengthCa affinity for

TnC

force

STROKE VOLUME (SV)

So: EDV SV!!!!!

Th t t i l fill i d t i t f


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CO = SV X HR

The amount a ventricle fills is a determinant ofventricular performance in the next beat

mL

Cardiac Cycle

mL

minute

Cardiac Cycles

min

EDV, EDPis preload


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Fluid in Pericardial cavity restricts ventricular filling due to

pressure on heart myocyte stretch ventricular

performance


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A(MV Closes)

B(AV Opens)

D(AV Closes)

E(MV Opens)

Volume

C

F

SV

A mitral valve closes (EDV)B aortic valve opens (DBP)

C peak systolic pressure (SBP)

D aortic valve closes (ESV)

E mitral valve opens (ventricular filling begins)

F maximal ventricular relaxation

SV = EDVESV

PV Loop Area = Total

ventricular WORK


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V

entricularPre

ssure,mmHg

Ventricular Volume, mL

A A

B B

C

C

DD

A

B

C

D

E EE

End-systolicpressure volumerelation

(ESPVR) CHANGE IN PRELOADONLY (EDV)

NOT CONTRACTILITY!

EDV SV

NO CHANGE IN ESPVR

(all points lie on the same

slope)


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Contractility


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****Shift from one curve to another

occurs with a change in myocardialcontractile state (contractility).***

Independent of EDV (filling)

Those circled in BLUE


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SympatheticNerves

CirculatingCatecholamines

Force-

Frequency

Inotropic

Agents (Digitalis)

IntrinsicDepression

Loss ofMyocardium

PharmacologicDepression

Anoxia,Acidosis

Those circled in BLUE

increase contractility!


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A

B

C

D

EVen

tricularPress

ure,mmHg


C

D

E

INCREASED

CONTRACTILITY:

NO CHANGE IN EDV!

Ca++sarcomere

activationforce

ESVSV

(remember: SV = EDV - ESV )

STEEPER ESPVR

SLOPE (NEW LINE)

ESPVR!!


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Filling changes:SAME ESPVR!

Contractility changes:shallower ESPVR!

(decreased contractilitydue to Verapamil)


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EJECTION FRACTION (EF):

EF = (SV) / (EDV)

Normally, the LV ejects between

55% - 65% of blood (EF)

A reduced EF usually indicates a

reduced stroke volumeusually

meaning that the heart is

FAILING. Once SV decreases

below ~30%, cardiac output

(CO) is also reduced, whichseverely impairs blood and

OXYGEN delivery to tissues, and

can result in ischemia and organ

death including MI!

SV = 100ml

EDV = 150ml ; ESV = 50ml ; SV = 100ml

EF = (100) / (150) 67%


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Filling causes PASSIVE increases

in force (pressure) due to CT

stretching during diastole (NO

CROSSBRIDGES ARE

FORMED)


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AfterloadAFTER AORTIC VALVE OPENS Afterload is the load onthe LV during EJECTION.

PRIMARILY DUE TO AORTIC PRESSURE (Paorta)or the

outflow resistance and slightly due to Total peripheral

resistance (ease at which blood can flow from aorta to tissues),

strongly influenced by VASOCONSTRICTION/DILATION @

the ARTERIOLAR level!!! (more to come on this later)


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Paorta afterloadESVSV (transiently!!!)

same amount of LV filling during diastoleEDV

SV (returns to previous level)

SV = EDV - ESV (both increased)

So: SV IS CONSTANT IN HEALTHY INDIVIDUALS!

NO CHANGE IN CONTRACTILITY! (SAME ESPVR)


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SV = EDV - ESV

EDV

ESV

SV

sv

SV


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A

B

C

D

EVent

ricularPressure,mmHg


C

D

EA

B

End-systolicpressure volumerelation

NO CHANGE INCONTRACTILITY!!!

MAINTAINCONSTANT STROKEVOLUME DUE TOSTARLINGS LAW!


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SV = EDV - ESV


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MyocardialDysfunction,Moderate

MyocardialDysfunction,

Severe

SV = EDV - ESV


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IN PATHOLOGICAL CONDITIONS (MYOCARDIAL

DYSFUNCTION)DEPRESSED VENTRICULAR FUNCTION:

An example that causes abnormal ventricular function is AORTICSTENOSIS (and also Hypertension).

The resultant narrowed aortic valve causes a chronically elevated

afterload for the LV, which causes the LV to develop more pressure inorder to pump the same amount of blood (in order to maintain SV).

HOWEVER: this also causes LV Hypertrophy, which is initially

beneficially because the heart is able to maintain CO. As the disease

process continues, hypertrophy now becomes detrimental to

ventricular function because the myocytes fail to stretch to normal

levels, which reduces the amount of filling, reducing EDV, and

ultimately leading to a severely reduced SVand of course leading to

ischemiathe common familiar outcome for LV heart failure.


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CARDIOVASCULAR

PHYSIOLOGY

Peripheral CirculationRoom 236; [email protected]


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Aortic

Pressure


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Systolic Blood Pressure (SBP):


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Systolic Blood Pressure (SBP):

1. Aortic stiffness (compliance)

2. SV

Diastolic Blood Pressure (DBP):

Ability of blood to flow to organs; peripheral runoff: the

pressure in the aorta just BEFORE the aortic valve OPENS!

PP = SBPDBP CO = (PaPra)TPR

MAP = DBP + (PP/3)

MAP = (CO) x (TPR) CO = MAP/TPR

CO = (SV) x (HR)

CO = (PaPra) x (r4) TPR = 8L

8L r4


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age stiffness

pressure for a given

volume!

Due to decreased elastic

properties of the aorta

THIS AFFECTS SBP!

SO: smaller increases in

volume will cause larger

increases in pressure as one

ages!


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1 2P-PQ=R


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Isolated HR:

peripheral runoffDBP

EDVSVSBP

PP Same MAP

Isolated SV:

SBPDBPPP

MAPCOperipheral runoff ; (HR

and TPR constant)

Combined SV, HR,

TPR (exercise):

See next slide


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(vasodilate)


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(Vasoconstriction@ arteriole

level)

CLINICAL CASE


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CLINICAL CASESubjective

Age 50Known heart murmurs

Objective164/56 mmHg; HR 72/minuteHeart murmursLeft ventricular enlargement

5-year-old male


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5-year-old maleBP 150/54L Precordial Lift

Continuous murmur

Increased PP because blood regurgitates back


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Increased PP because blood regurgitates back

into the LV decreasing DBP but the

increased volume in the LV increases SV increases SBP AORTIC REGURG!

SIMILAR for PDA, except that some blood is

flowing from aorta pulmonary artery then

being returned to the LV this causesdecreased DBP and increased SBP


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4

1 2(P - P ) r

Q or F =

8 L

Poisseuilles Law

1 2

P PQ R

4

8 LR =

r


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MeanPressure

DONT FORGET ABOUT

THE HEIGHT OF THE

COLUMN OF FLUID! INCREASED HEIGHT INCREASED PRESSURE

INCREASED FLOW!


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MAJOR DETERMINANT

OF RESISTANCE =ARTERIOLES!


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Parallel = reciprocal

addition increases

flow

Vs.

Series = additive

decreases flow

4P P r


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1 2P P rQ=

8 L

Decreasing the radius severely decreases flow: (4th power)


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Decrease radius (r) by causes flow to be reduced by 16!

(1/2) x (1/2) x (1/2) x (1/2) = 1/16

Ex) radius = 2 2^4 = 16

radius = 1 1^4 = 1

REMEMBER: CHANGING THE RADIUS AFFECTS BOTHRESISTANCE (TPR) AND FLOW (Q)!

So: since FLOW was decreased by 16, the resistance was increased

by 16. FLOW AND RESISTANCE ARE INVERSELY

RELATED!!!!!

REMEMBER: CO = MAP / TPR

I k hi b f i b h i h k f h

Session_2.ppt

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