Lecture 7: Regulation of cardiac function Flashcards
What are the determinants of stroke volume and thus cardiac output?
Preload
Afterload (Time for ejection)
Inotropic state
and thus Heart rate as it influences inotropic state and preload. (filling time and time for Ca reuptake)
What is lusitropy?
Relaxation of the myocardium (Ca removal)
What is dromotropy?
Conduction velocity of AV node
What are some key channels to be aware of in the myocyte?
L type Ca channel
RyR (JSR)
SERCA
NCX
Ca ATPase on cell membrane not SERCA.
Na/K ATPase
What is inotropic state?
Magnitude and rate of CA release from SR.
- Amount of Ca in SR (balance amongst fluxes)
- Inc. HR = Increased Ca and inotropy.
- Affinity of troponin C for Ca
-> Sarcomere length-dependent Ca sensitivity of troponin C (Frank starling mechanism)
What influences inotropic state?
- HR
- Length-tension relationship i.e frank starlings law
- SNS
How does the SNS enhance inotropic state?
Describe the signalling pathway and effects
Gs stimulates adenylate cyclase
- increased cAMP
- Increased cAMP dependent protein kinase A (PKA)
= Phosphorylation of
-> L type Ca channels
-> Phospholambam
-> RyR
-> Troponin 1
-> Other proteins
= Inc. L-type Ca channel opening, stimulation of SR and cell membrane Ca pumps, Faster Ca kinetics, Faster X bridge cycling.
More vigorous and rapid contraction (and relaxation)
What are the effects of parasymp on heart?
Muscunaric receptor
- Inhibits PKA formation
- Enhances Kir activity
Describe the force sarcomere length tension relationship in myocardiocytes
- No descending limb of relationship because high passive stiffness
- Steeper ascending limb because actin/myosin overlap
- Length dependent sensitivity of troponin C to Ca
Whats the deformation that occurs during the cardiac cycle?
Circumferential shortening
Longitudinal shortening
Torsion
Transmural shear
Radial wall thickening
Fibers arranged orthoganally.
What happens to myocyte shortening in heart failure?
Over time fractional shortening is reduced
Where are the ANS nerves found in the heart?
Vagus:PSNS: SA and AV node.
Cardiac SN: SA, AV and ventricular myocardium
Heterogenous distribution of PNS and SNS throughout the heart
How does SNS impact the heart? (Rate and Rhythm)
- Increased HR (~3s to take effect)
- Duration of cardiac AP reduced.
- Acceleration of impulse propagation through AV node
- May facilitate pacemaker activity of cells in the AV node
How does PSNS impact the heart?
- Reduced HR (Rapid)
- AP duration in atrial myocardium is reduced
- Deceleration of impulse propagation through the AV node
- Vagus nerve decreases inotropic state of atria (BUT less so on ventricles because of sparse innervation)
What determines oxygen supply to the heart?
- Perfusion pressure (aortic pressure and extravascular compression)
- Impedance (local auto-regulation)
= Coronary supply
To increase O2 supply must:
- Increased O2 conc.
- Increase blood flow.
What determines the oxygen demand of the heart?
- Basal metabolism
- Wall force development (Pressure*Time, Geometry (LaPlace)
- Inotropic state
- Heart rate
(Afterload)
Insert slide 28
plaease
What is coronary blood flow determined by?
Q = P / R
insert slide32
What determines local autoregulation of coronary vessels?
Active myocytes producing:
- Adenosine
- K, Pi, H, CO2
= Changes in osmolarity
Whats of note when it comes to the diastolic pressure time index vs tension time index?
In the healthy heart the coronary perfusion pressure * diastolic time > Systolic pressure * systolic time
i.e Supply>Demand
slide 34
What is happening to the myocyte in a hypoxic state?
Reduced ATP
= Reduced Na/K ATPase
= Hyperkalemia (inc. IKo)
= Reduced RMP
= Reduced AP upstroke speed and magnitude
= Shorted AP
= Reduced myosin head detatch
= Reduced NCX, SERCA
= Increased cytoplasmic Ca = impaired relaxation and filling = electrical instability
= reduced pH (acidosis), H competes with Ca on trop C
= Dec inotropic state and dec CO
= Reduced gap junction coupling etc (slows conduction)
etc
etc
