College aantekeningen Heart Failure & Therapy (AB_1211)

Lectures HFT

Lecture 1: Introduction heart function
- Tale of 2 circulations
o Pulmonary circulation lungs + heart
o Systemic circulation heart aorta organs
- Function of the heart
o Pumping deoxygenated blood to the lungs
o Pumping oxygenated blood to all the organs in the body
o Together with blood vessels providing adequate perfusion of all organs & tissues of the
body
o Main determinant of cardiac output contraction or relaxation?
 Relaxation is just as important as or more important than contraction
 Coordination is necessary to sustain cardiac output
- Excitation-contraction coupling
o Contraction of the heart following electrical stimulation of cardiomyocytes
- Automation of the heart
o The heart can beat independent of hormonal or neuronal input
o Spontaneous active
o Pacemaker cells
- Conduction through the heart
o Atrial excitation
 Begins in SA-node
 Ends in AV-node delays conduction with ±100 ms so atria and ventricles
don’t contract at the same time
o Ventricular excitation
 Begins in AV-node
 Through bundle of His
 Ends in bundle branches (left and right)
- Conduction between cardiomyocytes
o Electrically coupled
o Action potentials in cardiomyocytes
 SA node cells determine heart rate
 Unstable resting potential
 Slow depolarization prepotential  pacemaker potential
 Leaky for Na+/Ca2+ increase membrane potential/modulate heart rate
 Ventricular cells
 Stable resting potential ± -85 mV
 Quick depolarization influx of sodium
 Plateau influx of calcium
 Quick repolarization efflux of potassium
 Ion channel & action potential
o
o Basis for the resting membrane potential
 Membrane potential is determined by: concentration differences of ions &
permeability to ions
 Largely determined by K+ gradient high inside the cell
 Na+/Ca2+ high outside the cell
o Sympathetic stimulation
 During exercise maintain perfusion in times of increased demand
 Noradrenaline opens Na+/Ca2+ channels
 Quicker depolarization  steeper pacemaker potential
 Less negative resting potential

, o Parasympathetic stimulation
 Acetylcholine opens K+ channels
 Reduced slope
 Hyperpolarization
 Gets our heart rate at ±60-70
o Refractory period
 Period in which cells are inexcitable Na+ channels are not reset
 Absolute no action potential possible
 Relative needs very strong stimulant
 Key to contraction-relaxation behavior of cardiomyocytes
o Excitation-contraction coupling
 Link between membrane depolarization and contraction
 Calcium induced calcium release
 To contract  need to increase Ca2+  Ca2+ binds to myofilament
power stroke can happen
o Force development of cardiomyocytes
 Amount of intracytosolair calcium
 Ca2+ sensitivity of contractile apparatus
- Single heartbeat at cellular level
o Electrical signal from neighboring cell
o Action potential Na+ influx Ca2+ influx K+ efflux
o CICR calcium induced calcium release
o Ca2+ binds to myofilaments
o Power stroke cell shortening
o Ca2+ release from myofilaments
o Reuptake in SR relaxation
- Pump function of the heart
o Excitation-contraction coupling
o Single heartbeat
 Systole  contraction
 Diastole relaxation




o Ventricular cycle 4 phases
 Filling
 Outlet valves closed
 Inlet valves open

,  Blood goes where pressure is lowest
 Atrial boost before ventricular contraction
o More important in exercise/increase in age
 Isovolumetric contraction
 Outlet valves closed
 Inlet valves closed
 Buildup pressure
o Not yet higher than in vessels would flow back in ventricle
 Ejection
 Outlet valves open
 Inlet valves closed
 Isovolumetric relaxation
 Outlet valves closed
 Inlet valves closed build pressure in atria
o Relationship between pressure, volume and ECG
 Pressure in LV, LA and aorta




o Ventricular volume changes

, o Stroke volume
 End diastolic volume – end systolic volume
o Ejection fraction
 Stroke volume / end diastolic volume
 ± 67% in healthy people
 < 45%  systolic dysfunction
o LV vs RV
 Equal stroke volume
 Pressure lower in RV lower resistance in lungs
 Less muscle needed  thinner wall RV
o Pressure volume loop other way to describe cardiac cycle
 Volume vs pressure of the LV




o Heart valves
 Between atria and ventricles
 Right tRicuspid
 Left mitraL
o Heart sounds
 1st heart sound systole
 Closing mitral and tricuspid valve
 Low pressure, low frequency
 2nd heart sound diastole
 Closing of aorta and pulmonary valves
 High pressure, high frequency
 Sound in between not good leaky
o Cardiac output (ml/min)
 Stroke volume (ml) * heart rate (/min)
 Handling increase
 Heart rate
o Central nervous system sympathetic effects on SA node
o Hormones (nor)adrenaline/thyroid hormone
 Stroke volume
o End-diastolic volume pre-load (Frank-Starling mechanism)
 Increased filling pressure leads to increased stroke
volume more blood  pumps harder