Flashcards in Acute Cardiac Adaptations Deck (26):
What ion needs to be properly handled to maintain contractile performance at the myocyte and myofibril level?
• Calcium handling and calcium sensitivity are super important
Where is SERCA2 located?
• In the LONGITUTIDINAL SR, not the junctional SR
• This is important because they are not super close to the L-type calcium channel action
What factors influence EC50?
• EC50 is the concentration at which cardiac muscle is 50% contracted
• It's a way of monitoring calcium sensitivity
• Sarcomere length
• Contractile protein phosphorylation
Troponin I is phosphorylated by what two "PK" enzymes?
• PKA and PKC
• PKA sites will increase velocity of contraction
• PKC sites decrease velocity of contraction
What does the curve of Active tension vs. initial muscle fiber length look like?
• Active tension would be on the Y axis here and fiber length on x-axis
• Fiber length is the same as preload
• This is the starling curve
• It's a 45 degree line (positive slope) until an exponential drop off
• Increasing length directly increases tension to a certain point
Does increasing sarcomere length increase or decrease EC50?
• Decrease. Stretching the sarcomere increases calcium sensitivity
• The molecular mechanism by which stroke volume is increased on the next beat after there is increased preload and thus stretch/tension of the myofibril
Norepinephrine will have what effect on muscle contractility?
• It shortens the myofibrils, it enhances contractility
• At shorter muscle lengths are higher muscle tensions (compared to without NE)
What does phosphorylation due to beta adrenergic stimulation of SAN Ca channels do?
• Increases heart rate
• Increases cardiac output
What does phosphorylation due to beta adrenergic stimulation of ventricular cell Ca channels do?
• Increase calcium entry
• Increase force of contraction
Improves ejection fraction by increased inotropy
What does phosphorylation due to beta adrenergic stimulation of sodium pump do?
• NCX, increases calcium efflux
• Enhances relaxation and diastolic filling
What does phosphorylation due to beta adrenergic stimulation of troponin I do?
• The inhibitory troponin
• Lowers calcium affinity for TnC
• Increased lusitropy, increased relaxation
What does phosphorylation due to beta adrenergic stimulation of FKB do?
• Enhances Ryr receptor mediated calcium release
• Enhances contractility for greater stroke volume
What does phosphorylation due to beta adrenergic stimulation of phospholamban do?
• PLB phopsphorylation will disinhibit SR calcium pump SERCA2
• Increases SR calcium load
• Improved diastolic filling (lusitropy)
What does the heart do when we go to the gym?
• Decrease peripheral vascular resistance
• Increase venous return
○ Leads to greater cardiac output through frank-starling
• Increase heart rate
• Increase inotropy
Isometric excersise (weight training) will have what effect on the CV system?
• It will INCREASE peripheral vascular resitance
○ Idea is to funnel flow to excercising muscle group
• Increases HR, but does not increase CO because total venous return is not increased (but HR is)
What happens right after a myocardial infarction?
• Loss of functional myocardium
• Increased catecholamine surge
○ Sweating, tachycardia, hypertension?
• Increased inotropy to maintain CO despite the blood pressure
○ Accomodating afterload
• Heterogenous cellular environment
○ Changes in pH, membrane potential and secondary effect on cytosolic calcium
The response to acute changes in hemodynamic and adrenergic stimuli look like what?
• Altered P/V relationships
• Altered inotropy
• Altered chronotropy
When the heart adapts by increasing myocyte length way out of proportion with width, extensive fibrosis, myocyte death, and advanced cardiac dysfunction, what do we call that disease?
• Dilated Cardomyopathy
• Can be caused by MI
The heart responds in what way to chronic hypertension and/or aoric valve stenosis?
• Pathological hypertrophy
• Myocyte length increases, but the width REALLY increases
• Cardiac dysfunction likely
An MI can cause DCM. What is that?
• Dilated Cardomyopathy
• When the heart adapts by increasing myocyte length way out of proportion with width, extensive fibrosis, myocyte death, and advanced cardiac dysfunction
Is a gross change in heart size and function only a visual change or is there a difference at the cellular level?
• There is certainly a difference at a cellular level
• There can be myosin isoform switches and ATPase expression changes in phenotypically distinct models of cardiac hypertrophy
What might an increase in ATPase and alpha-alpha Myosin Heavy Chain be indicative of?
• Physiologic (not pathologic) hypertrophy
What might a decrease in ATPase but an incrase in beta-beta Myosin Heavy chain be indicative of?
• Pathological hyperothrophy
What is the contemporary view of heart changes in chronic heart problems adaptation?
• Though the heart remains terminally differenctiated, there are dynamic changes that occur at the celular level
• Involves architectural and biochemical modifications
• Stress modifies quantitiy and quality of contractile elements
• Programmatic alterations in gene and protein expression occur in response to pathologic or physiologic triggers
What is likely going on in a cell that is part of Left ventricular hypertrophy?
• Increase in PLB to SERCA ratio
• Increase in calcium intracellular
• Incrase in L-type channel activation
• Overall impairment in relaxation and the calcium steady state is changed