Chronic Cardiac Adaptation Flashcards Preview

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Flashcards in Chronic Cardiac Adaptation Deck (12)

What will a patients heart look like who has had chronic hypertension or aortic stenosis?

=Pathologic hypertrophy
-increased size, fibrosis, maybe dysfunction


What will happen to a heart in response to an infarction or chronic hypertrophy?

=Cardiac dilation
-myocyte length >> width
-extensive fibrosis
-myocyte death
-advanced dysfunction


Describe the myosin heavy chain isoforms

All myosin chains are heterodimers of any combination of alpha/ beta MHC isoforms
-Ratio of isoforms varies across species
-they are from different genes
-transcriptionally regulated


In an elite athlete, how would their myosin isoforms and ATPase differ from pathologic hypertrophy

Physiologic: increased ATPase and aa MHC
-alpha always has higher ATPase (10/1)
Pathologic: decreased ATPase and bb MHC


T/F: the heart can adapt through both architectural and biochemical modifications?

phenotypic/ genotypic plasticity
-both transcriptional and post-translational!


What are the cellular mechanisms of left ventricular hypertrophy?

-Increase in Ca current in L-type calcium channels
-reduced SR pump fxn (high PLB/ Serca2 ratio)
-impaired myofilament relaxation
-increased cytosolic Ca


Just be aware that you see different cascades, modifications, etc as the insult becomes more chronic

Over time different kinases and transcription factors result in different effects


How does chronic heart failure usually begin?

Left ventricular hypertrophy
-pressures increase, and stroke volume decreases


What are some proposed targets to correct heart failure?

SERCA2 - worked in animals, failed in humans
Calcineurin - phosphatase, triggered by increased Ca
-phosphorylates NfAT which alters transcription


Jerry had a heart attack and wants to know if he will recover. What could happen to his heart

Well based on the POSITIVE FEEDBACK mechanism he talked about in class, after major insult the LV decreases in function as the severity is amplified over time


What is the viscous cycle leading to heart disease?

External signal > G coupled proteins
>> negative Ca fluxes + kinase/phosphatase activity
>>> changes in myofilament & transcription activity
>>>> Cardiac remodeling and growth & myofilament problems

(just understand concept)


In conclusion whats the end result of the positive feedback mechanisms of CHF

= self propagating mechanisms progressing to pathology

Muscle damage or stress > pump dysfunction > decreased CO > cycles through neurohumoral activation, apoptosis, remodeling > edema, tachycardia, congestion