Chronic Cardiac Adaptation

Question 1

Cardiac dilation

Answer 1

Myocyte length increase&raquo_space; myocyte width increase
Extensive fibrosis
Myocyte death
Advanced cardiac dysfunction

Question 2

Pathological hypertrophy

Answer 2

Myocyte length increase < myocyte width increase
Fibrosis
Maybe cardiac dysfunction

Question 3

Physiologic hypertrophy

Answer 3

Myocyte length increase > myocyte width increase
No fibrosis
No cardiac dysfunction

Question 4

What types of MHC exist? What do they form and how do they differ?

Answer 4

There are alpha and beta isoforms
Form heterodimers (aa, ab, and bb) 
Have distinct ATPase activity (and some other functional properties)

Question 5

Biochemical property of pathological hypertrophy

Answer 5

Decrease in ATPase and increase in bb MHC

Question 6

Biochemical property of physiological hypertrophy

Answer 6

Increase in ATPase activity and aa MHC

Question 7

The heart has not only _____ plasticity but also _____ plasticity

Answer 7

phenotypic, genetic

Question 8

The functional adaptations of the heart are generally ____ but can result in ventricular dysfunction over time

Answer 8

adaptive

Question 9

LVH –> CHF phenotype

Answer 9

Heart becomes more stiff, concentrically hypertrophied = pathologic hypertrophy

LVH:
At same EDV, less CO because heart is ejecting against increased afterload

CHF:
As heart fails, PV curve shifts right (dilated cardiomyopathy)

Question 10

Cellular mechanisms of LVH

Answer 10

1. Increase in Ca current via L-type Ca channel
2. Reduced SR pump fxn via increased PLB/SERCA2 ratio
3. Impaired myofilament relaxation
4. Altered (increased) cytosolic calcium and new steady-state

Question 11

____ gene transfer is sufficient to correct mechanical defects in cadiocytes from animals with HF

Answer 11

SERCA2

Question 12

Calcineurin & NFAT to demonstrate that genes really can lead to LVH or other remodeling

Answer 12

Calcineurin dephospho NFAT
NFAT translocates into nucleus & influences gene transcrption ofcardiac growth and remodeling genes = some master regulatory switches.

Question 13

Explain the animal testing of LV function following an acute insult

Answer 13

Give animal heart attack
EF drops, heart function fails…
Over time things got worse despite attempts to use P4H

Why? Series of positive feedback loops. If you don’t do something to interrupt them, you will see progressive decline in cardiac fxn. Current therapy is trying to interrupt.