Regulation of Cardiac function Flashcards
Deteminants of CO (diagram)
HR x SV SV= EDV-ESV ^HR= ^ inotropy (less calcium extruded, thus increased inotropy), decrease of preload when very high Higher preload, higher EDV and thus SV ESV altered by inotropy and afterload Increase in afterload, decrease in SV
Pressure volume relation and preload, afterload and inotropic state
Preload: increase SV, as further along due to larger EDV, increased LV pressure generated
Afterload: Increased systemic pressure, means less ejection from heart (follow pressure linear line). (less SV)
Note is not just systemic pressure, but tension/stress on heart cells
Inotropy: increase- increased gradient of line, lower ESV thus increase in SV. decrease, lower gradient, higher ESV.
Inotropy, chronotropy, lusitropy, dromotropy
Inotropy: myocardium contractility (calcium)
Chronotropy: SAN firing rate, thus HR
Lusitropy: myocardial relaxation (Calcium removal)
Dromotropy: conduction velocity of AVN
Revision of cardiac myocyte and calcium movement
AP triggers L type calcium channels, calcium influx. (T-tubule)
Binds to RyR on JSR. Causes Calcium release from SR
Calcium binds troponin C, exposesactin and cross-bridge cycling
Removal: SERCA into the SR; Ca ATPase in sarcolemma; NCX: passive extrusion. Calcium inflow during AP, plateau of AP calcium removal
What is inotropic state regulated by in the myocyte?
Magnitude of Calcium in SR + rate of release on activation
Affinity of troponin C for Calcium- sarcomere length dependent sensitivity
SNS effect on myocytes: what receptor? What effects?
end result
note spread throughout heart and AVN/SAN; sides, right side effects SAN, left more associated with contractility
NE and E bind to B1 receptor, which is linked to a GPCR Gs.
Increases cAMP and PKA, leading to phosphorylation of:
L-type calcium channels: increase duration of opening, more calcium in, increased inotropy.
Phospholamban: Increases SERCA, so quicker relaxation
RyRs: increased calcium sensitivity
Troponin I: faster X bridge cycling
More vigorous+rapid contraction and relaxation
PNS effects on myocytes
note both PNS and SNS ____ AP duration
effects primarily atria
M2 receptor linked to Gi
Less cAMP, less PKA, less phosphorylation
Less vigorous and less rapid
Opens K+ channels via By subunit-Increases the I(Kr)= rapid repolarisation.
Shortened (in atrial myocardium)
decreased impulse propagation through AVN
decreases inotropy in atria, less so than ventricles
Force length relationship with cardiac and skeletal muscle
Skeletal muscle: ______ limb, _____, ______ limb. Increase in length increases ____, plateau then decreases
Cardiac comparatively, is on the same scale but has no _____ limb, and a _____ ascending limb.
No descending limb because of ___ ____ _____ of heart (will not stretch much, does over long time e.g HF)
Steeper ascending limb because of actin myosin overlap PLUS _______________.
Skeletal muscle: Ascending limb, plateau, descending limb. Increase in length increases force, plateau then decreases
Cardiac comparatively, is on the same scale but has no descending limb, and a steeper ascending limb.
No descending limb because of high passive stiffness of heart (will not stretch much, does over long time e.g HF)
Steeper ascending limb because of actin myosin overlap PLUS length dependent affinity of troponin C.
Result of a hypoxic state in myocardium at a cellular level
-Reduced Na+/K+ ATPase activity, therefore reduced gradients (more sodium in cell, and more potassium outside cell)
HYPERKALAEMIA: Less negative RMP; reduced AP upstroke; shortened AP duration; reduced NCX (calcium build up)
-reduced myosin head detachment, impairing relaxation
-reduced SERCA, impaired relaxation as increased calcium. electrical instability
-reduced pH- ACIDOSIS. H+ competes with Calcium on tropononin C, reducing inotropy and reduced nexus junctioning.
Deformation of cardiac myocytes during contraction
Circumferential shortening; longitudinal shortening; torsion; transmural shear
= radial wall thickening
Muscle in layers, all orientated differently. Axis changes on contraction.
In hypertrophied hearts, more collagen in cleavage planes, and less sliding together. No laminar structure. Loss of structure. Hypertensive heart failure
SNS effect on cardiac cycle (5)
- Atrial contraction pressure increases
- Rate of LV pressure development is increased, as is LV pressure
- Initial acceleration of blood ejected increased, as is max level of aortic flow
- Ventricular ESV is reduced, thus SV increases
- Rapid filling occurs faster and somewhat sustains ventricular filling
Which has a stronger effect on heart rate? SNS or PNS
PNS is more in control can override the SNS due to Ach release and binding being faster, and cAMP second messenger systems is slower. PNS will cause potassium channel binding, faster.
Also AChE, NE must be reuptaken (a2 receptor?)
Determinants of myocardial oxygen DEMAND
-Basal metabolic rate: energy to turnover cellular processes and maintain organelle systems
-Wall force development: force is proportional to the pressure generated (time important paramter) + geometry.
Geometry: LaPlace law, dilatation requires increase energy to maintain LV pressure. This is dependent on afterload
-Inotropic state: generating greater force, alters XBC and SERCA, and thus ATP
-HR: related to inotropy
Determinants of myocardial oxygen SUPPLY
- Oxygen delivery, which is equal to flow rate x (CaO2-CvO2, oxygen extraction). Thus to increase, increase CaO2, decrease oxygen extraction, increase blood flow
- Perfusion pressuredriving blood around
- Impedance, resistance to flow of vessels (local auto regulation)
Coronary blood flow
Left versus right side
When is it highest and what does it follow?
Myocyte relation
control
- Left has more flow, highest in diastole and then follows aortic pressure down. In systole are compressed.
- Diastole
- Dense vasculature, when roughly each myocyte has its own capillary
Thus higher heart rate, shorter diastolic interval
dtermined by roughly aortic root pressure- LV lumen pressure
Local control, vasoactive metabolites causing VD when working hard to reduce resistance, some neural/hormonal
