Flashcards in Chronic Cardiac Adaptation Deck (12)
What will a patients heart look like who has had chronic hypertension or aortic stenosis?
-increased size, fibrosis, maybe dysfunction
What will happen to a heart in response to an infarction or chronic hypertrophy?
-myocyte length >> width
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
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)