Flashcards in Regulation of cardiac function - LeGrice Deck (25):
Draw the map for the determinants of cardiac output
Draw the pressure volume curve and the subsequent curves with
- effect of preload
- effect of after load
- Effect of inotropic state
contractility of myocardium (calcium)
firing rate of SA node (heart rate)
relaxation of myocardium (calcium removal)
conduction velocity of AVN
What determines after load?
not just the arterial pressure, but also the stress in the wall determined by the geometry of the heart and the pressure its generating
cardiac inotropic state depends on?
magnitude and rate of calcium release form the SR on activation (depends on amount of calcium stored in the SR, which in turn depends on the balance between different fluxes)
The affinity of troponin C for Ca2+ ions
effects of sympathetic activation on the cardiac muscles inotropic state
adrenaline and noradrenaline actions are exerted by the beta1 receptor which activates the Gs protein which stimulates adenylate cyclase, inc cAMP, cAMP dependant protein kinase A = phosphorylation of L type calcium channels, phospholambin, ryanodine receptors, and troponin I, etc. = increased opening of L type calcium channels, stimulation of SR and membrane Ca2+ pumps, faster Ca2+ kinetics and faster X bridge cycling.
= increase in magnitude and rate of calcium release from SR on activation
Effect of the PNS on cardiac myocyte inotropy
actions of acetylcholine mediated via the M2 muscrainic receptoractimating Gi which inhibits adenylate cyclase = decreased cAMP.
Gi also directly opens K+ channels via the beta-gamma subunit = decreased action potential duration
force length relationship for cardiac vs skeletal muscle sarcomeres
no descending limb because cardiac connective tissue limits sarcomere length
Steeper for cardiac than skeletal muscle because extra length sensitivity of length dependant affinity of troponin C for Ca2+ ions in cardiac muscle
Effect of hypoxia
Reduced ATP = reduced Na+/K+ pump
- Reduced Na+ and k+ transmembrane concentration gradient
- hyperkalemia (inc [K+]o)
reduced relating membrane potential
- reduced action potential upstroke speed and magnitude - shortened APD
- reduced Na+/Ca2+ exchange
Reduced myosin head detachment (ATP required for relaxation)
Reduced sarcolemmal Ca2+ extrusion = increased cytoplasmic Ca2+
- Impaired relaxation / filling
- electrical instability
Reduced pH = acidosis
- H+ competes with Ca2+ on troponin C = reduced inotropic state
- reduced nexus junction coupling
myocyte axis -60degrees at epicardium through to 90+ degrees at endocardium
the 3D patterns of the heart wall deformation and motion that occur throughout the cardiac cycle cannot be equated to the axial length changes of myocytes.
- circumfrumential and longitudinal shortening, ventricular wall thickens rapidly
- dimensional changes greatest at endocareidal surface and least at epicardial surface curcumfumential shortening greater than longitudinal shortening
shortening in myofiber length remarkably uniform
local shear deformation involving slippage or relative movement of layers of cells
describe the types of remodelling of ventricles in structural heart disease
Systemic hypertension --> LV myocyte hypertrophy and wall thickening and a marked increase in collagen density throughout the LV thus increasing LV stiffness in diastole reducing effectiveness of cardiac filling
The origin and distribution of cardiac nerves
Parasympathetic nerve terminals are often close to sympathetic adrenergic terminals in the heart, NE inhibits the release of ACH and vice versa
sympathetic regulation of cardiac function effects on:
- inc HR response is relatively slow with latency of 1-3 secs and 30 secs taken to reach steady state
- Duration of AP reduced, acceleration of impulse propagation through the AVN
- increases inotropic state of atria and ventricles
L sympathetic fibres have more effects on contractility than right sympathetic fibres while those on R have greater effect on heart rate.
Parasympathetic regulation of cardiac performance effects on?
- reduces HR, rapid in comparison to the effects on sympathetic stimulation
- action potential duration in atrial myocytes reduced, deceleration of propagation through the AVN
- decreases inotropic state of the atria
- effects on ventricular inotropic state much less reflecting sparse PNS innervation of ventricles
Complete autonomic blockade is associated with
Increase in resting HR to 105bpm and reduction in cardiac inotropic state.
At rest there is vagal suppression of HR but sympathetic maintenance of contractile state
Parasympathetic division seen as the dominant controller of HR, effects precise moment to moment adjustments
whereas sympathetic cardiac nerves effect dominant control over cardiac inotropic state.
The rate of SNS and PNS responses
- The SA and AVN nodes are rich in cholinesterase thus Ach released at nerve terminals is rapidly hydrolysed so the effects of vagal stimulation decay rapidly
- Response to Ach rapid because the receptors it binds to (M2) send a G protein directly to channels to illicit action.
- Noradrenaline released from nerve terminals at relatively slow rate and cellular response mediated through relatively slow cAMP second messenger systems
- Termination of response is slow because mechanism is presynaptic terminal reuptake and removal by blood.
What are the determinants of myocardial oxygen consumption?
metabolic cost of maintaining cell organelle systems and activation of contractile process (small)
MURAL FORCE DEVELOPMENT
magnitude of wall force development directly related to pressure generated in contraction and geometry of ventricle, if the LV is dilated, wall force development required to produce a given LV pressure is greater than normal.
Myocardial oxygen demand measured by magnitude and time of force
changes in this alter number and rate of interactions between contractile proteins, thus changing magnitude and duration of wall force development.
Changes in HR tend to be linked to changes in the inotropic state and therefore their values don't change independently
myocardial oxygen requirements can be met by?
increasing arterial oxygen content
increasing coronary oxygen extraction
increasing coronary blood flow
Normal circumstances: arterial blood near completely saturated, oxygen extraction form the coronary circulation is substantial therefore oxygen supply must be matched to demand mainly by changes in coronary blood flow.
coronary blood flow changes during diastolie and systolie
Isovolumetric contraction = cessation of blood flow due to compression of vessels
Sytolie = some recovery, flow still relatively low
Isovolumetirc relation = blood flow rebound as extravascular compression released
Diastolie = flow follows that of aorta
What sets that relative duration of blood flow to the left ventricular subendocardium?
the difference between aortic and left ventricular pressures,
= the diastolic interval
the amount by which it is possible to increase blood flow
about 100mL/min/100g under exercise can go unto 450mL/min/100g
If coronary perfusion pressure reduced by atherosclerotic narrowing or if oxygen demand abnormally high reserve may be exhausted.
Reserve appears to be most limited in the subendocardial region. Inc HR will decrease BF and hence dec CR.