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Flashcards in how does heart work 2 Deck (31):
1

Length dependency of a muscle:

1. the longer the muscle is: the more force it generates.
2. In isolated muscle fibers and also in the heart.
3. This is called the preload dependency.

2

Integrated cardiac performance:

1. pressure volume loop.
2. When cardiac muscle LV increases volume, the amount of blood ejected increases

3

PKA functions to

1. phosphorylate TnI and influences actin and myosin relationship to allow for more actin and myosin interactions can take place ,
2. also increase the amount of Ca influx from the Ca2+ channel
3. PKA inhibits PLB, which inhibits SERCA, to allow for CA2+ to cycle out of the SR more rapidly.

4

B adrenergic signal causes

an increase in extracellular ca2+ AND intracellular Ca2+

5

Major coordinate responses of hear muscle to beta adrenergic stimulation:

phosphorylation of:
1. Ca channels (SAN cells)
2. Ca channels (ventricular cells)
3. Na pump
4. phospholamban
5. FKB
6. troponin I

6

phosphorylation of Ca channels (SAN cells) will result in

1. ↑ Heart rate
2. Improved CO
(CO=HR x SV)

7

Phosphorylation of Ca channels
(ventricular cells) will result in

1. ↑ Ca entry
2. ↑ Force of contraction
3. improved EF (+ inotropy)

8

Phosphorylation of Na pump
will result in

1. ↑ Ca efflux (via Na-Ca exchange)
2. Enhanced relaxation and diastolic filling

9

Phosphorylation of Phospholamban will result in

1. Disinhibition of SR calcium pump (SERCA2)
2. Increased SR calcium load
3. improved diastolic filling

10

Phosphorylation of FKB
will result in

1. Enhances Ryr receptor mediated calcium release
2. enhanced contractility

11

Phosphorylation of troponin I
will result in

1. ↓ Ca affinity for TnC
2. enhanced relaxation

12

bigger hearts result in

bigger contractions

13

SV is a measure of

end diastolic volume
because of the length/tension relationship

14

short contractions (muscle shorter) means the interactions between myosin and actin are

less

15

big contractions (muscle longer) means the interactions between myosin and actin are

greater

16

muscle can increase force of contraction by

1. getting longer
2. if exposed to inotrope and shift Frank starling curve

17

myosin alpha vs beta

α myosin has greater ATPase activity than β

this means that α has more activity, so it would be more prevalent in a mouse, whose heart beats 400 times a minute (all alpha) , than in an elephant whose is more like 40 and would have all β

18

ATPase is proprtional to

resting HR per minute

19

how does LV hypertrophy lead to Chronic HF?

1. heart develops LVH, decrease CO because heart is ejecting against an increased afterload
2. heart falls apart, the frank starling curve shifts down
3. volume increases and the ability to eject decreases

20

LVH : Cellular mechanisms

1. Likely increase in Ca current via
L-type Ca channel
2. Reduced SR pump fxn
(↑ PLB/SERCA2 ratio)
3. Impaired myofilament relaxation
4. Altered (increased) cytosolic calcium and new steady-state
5. post transcriptional and post translational modifications

21

LVH: Early/acute modification:


1. PKA
2. PKCβ

22

LVH: Late/Chronic modification:

1. PKCε / PKD
2. CAMκ
3. calcineurin

23

triggers for LVH are

1. neurohormonal modulators
2. genetic factors
3. exercise
4. stretch
5. hypertension

24

Hypertrophic remodeling results in

1. ↑βMHC
2. ↑ ANF
3. ↓ αMHC
4. ↓ SERCA2

25

Hypertrophic heart is not only different in the appearance, but it also

handles calcium differently and signals differently

26

Calceneurin

1. is activated by calcium
2. It is a phosphatase.
3. It takes a super long time (hours) for it to be activated.
4. When it becomes activated,it dephosphorylates Nfat and nfat is activated and it goes into the nucleus.

27

how can you make a mouse have dilated cardiomyopathy?

1. dephosphorylate NFAT or
2. chronically activate calceneurin,
3. they contract poorly and have txn factors like human with dilated cardiomyopathy

28

______ is one of the key markers in dilated cardiomyopathy

Increase in cytosolic calcium

29

Adaptations to a chronic load is

complex, coordinated and involved changes at the txn level which cause the heart to be reconfigured.

30

How do you measure heart function?

using ejection

31

progressive decline in cardiac function after a heart attack results from

a series of positive feedback loops

it takes a big hit.
Progressive cardiac dysfunction from the lack of positive feedbacks