Inhoud
Physiology of the cardiovascular system................................................................................................. 2
Diabetes and obesity and vessel function ............................................................................................... 8
Introduction to heart failure ................................................................................................................. 16
Translational studies in cardiomyopathies............................................................................................ 23
Gene regulation in the cardiovascular system ...................................................................................... 25
Bench to bedside research in hypertrophic cardiomyopathy: engine and energy ............................... 32
Animal models of cardiomyopathies..................................................................................................... 36
Pulmonary arterial hypertension .......................................................................................................... 40
Inherited cardiomyopathies – clinical perspective ............................................................................... 46
The Hoorn studies ................................................................................................................................. 50
Cellular ageing ....................................................................................................................................... 53
Atrial fibrillation .................................................................................................................................... 62
Begrippen .............................................................................................................................................. 69
,Physiology of the cardiovascular system
Function of the heart
- Pumping deoxygenated blood to the lungs
- Pumping oxygenated blood to all the organs in the body
- Together with blood vessels: providing adequate perfusion (doorbloeding) of all organs and
tissues of the body
Cardiac output is determined by contraction and relaxation of the cardiomyocytes
Excitatie-contractie koppeling = de contractie van een hartspiercel volgt op de elektrische stimulatie
van die cel: excitation first then contraction
This works because there is automation in the heart; the heart beats independent of hormonal and
neuronal input/ no active input.
Het hart kan automatisch (spontaan/actief) zelfstandig samentrekken want in de afwezigheid van
hormonale of neurale stimulatie kunnen pacemakercellen in de sinusknoop een actiepotentiaal
veroorzaken, deze verloopt langzaam en begint met een prepotentiaal. Als de drempelwaarde wordt
overschreden vind het actiepotentiaal plaats.
Pacemaker cells produce an electrical signal, this consists of action potentials. Pacemaker cells have
specific action potentials, there is a rhythm in the action potentials, our heart rhythm
,The rhythm works with three ions and three channels
1. Sodium Na: high outside low inside +
2. Calcium Ca: high outside low inside +
3. Potassium K: high inside low outside +
During rest sodium channel is open and allows sodium to enter the cell, this will make the membrane
potential more positive, this is a slow process. Sodium enters until the threshold (-40 mV) is reached.
-40 mV or higher → calcium channel will open, making the membrane potential more positive until a
certain value → potassium channels will open → potassium moves out of the cell making the
membrane potential lower again
The ions move through the channels via the concentration gradient = passive transport
The threshold value cannot be regulated, is always the same (-40 mV)
Heart rate is determined by
- Resting membrane potential of SA node cells:
voor hogere frequentie wordt het rustpotentiaal verhoogd zodat de drempelwaarde eerder
bereikt wordt
- Velocity of depolarisation: slope (helling) of the prepotential:
voor hogere frequentie moet de helling van het prepoteniaal steiler worden. Dit wordt
gedaan door de natriumkanalen wijder open te zetten. Dit gebeurt door Noradrenaline
o Increasing heart rate: Noradrenaline (NA) → open sodium channels wider
- Snelheid van repolarisatie:
voor een lagere frequentie moet de daling sneller gaan door de kaliumkanalen wijder open
te zetten
o Decreasing heart rate: Acetylcholine (Ach) → opens potassium channels
Cardiomyocytes (hartspiercellen) only undergoes an action potential when a neighbouring
cardiomyocytes undergoes
Difference:
- Sodium entry is very quick, no pre-potential, quick rising potential. Open and close quick
- Slow rise in calcium
- Finally potassium channels open → repolarisation
, Cardiomyocytes have a very quick but long-lasting action potential
Calcium is important to induce contraction, Calcium concentration has to increase inside your cell
Excitation → sodium and calcium are entering inside your cell, but not enough, → calcium induced
calcium release = organel filled with calcium (sarcoplasmic reticulum calcium - SRCa) , calcium binds
and make this organel release about 10 times more calcium →calcium will bind to contractile
proteins → contraction of CMs
SRCa pumps calcium back into the organel (requires energy)
Contraction:
During rest myosin can’t bind to actin because there are other proteins that block it (tropomyosin) →
Calcium bind to .. complex shifts tropomysin → myosin can bind to actin → myosine kop buigt en
beweegt het actine (powerstroke) → hartspiercel spant aan
ATP is needed to release
Calcium is removed → binding stops
Conduction system
1. Start: sinoatrial (SA) node
2. AV node = delays the signal
3. AV bundle
4. Bundle branches
5. Purkinje fibres
Physiology of the cardiovascular system................................................................................................. 2
Diabetes and obesity and vessel function ............................................................................................... 8
Introduction to heart failure ................................................................................................................. 16
Translational studies in cardiomyopathies............................................................................................ 23
Gene regulation in the cardiovascular system ...................................................................................... 25
Bench to bedside research in hypertrophic cardiomyopathy: engine and energy ............................... 32
Animal models of cardiomyopathies..................................................................................................... 36
Pulmonary arterial hypertension .......................................................................................................... 40
Inherited cardiomyopathies – clinical perspective ............................................................................... 46
The Hoorn studies ................................................................................................................................. 50
Cellular ageing ....................................................................................................................................... 53
Atrial fibrillation .................................................................................................................................... 62
Begrippen .............................................................................................................................................. 69
,Physiology of the cardiovascular system
Function of the heart
- Pumping deoxygenated blood to the lungs
- Pumping oxygenated blood to all the organs in the body
- Together with blood vessels: providing adequate perfusion (doorbloeding) of all organs and
tissues of the body
Cardiac output is determined by contraction and relaxation of the cardiomyocytes
Excitatie-contractie koppeling = de contractie van een hartspiercel volgt op de elektrische stimulatie
van die cel: excitation first then contraction
This works because there is automation in the heart; the heart beats independent of hormonal and
neuronal input/ no active input.
Het hart kan automatisch (spontaan/actief) zelfstandig samentrekken want in de afwezigheid van
hormonale of neurale stimulatie kunnen pacemakercellen in de sinusknoop een actiepotentiaal
veroorzaken, deze verloopt langzaam en begint met een prepotentiaal. Als de drempelwaarde wordt
overschreden vind het actiepotentiaal plaats.
Pacemaker cells produce an electrical signal, this consists of action potentials. Pacemaker cells have
specific action potentials, there is a rhythm in the action potentials, our heart rhythm
,The rhythm works with three ions and three channels
1. Sodium Na: high outside low inside +
2. Calcium Ca: high outside low inside +
3. Potassium K: high inside low outside +
During rest sodium channel is open and allows sodium to enter the cell, this will make the membrane
potential more positive, this is a slow process. Sodium enters until the threshold (-40 mV) is reached.
-40 mV or higher → calcium channel will open, making the membrane potential more positive until a
certain value → potassium channels will open → potassium moves out of the cell making the
membrane potential lower again
The ions move through the channels via the concentration gradient = passive transport
The threshold value cannot be regulated, is always the same (-40 mV)
Heart rate is determined by
- Resting membrane potential of SA node cells:
voor hogere frequentie wordt het rustpotentiaal verhoogd zodat de drempelwaarde eerder
bereikt wordt
- Velocity of depolarisation: slope (helling) of the prepotential:
voor hogere frequentie moet de helling van het prepoteniaal steiler worden. Dit wordt
gedaan door de natriumkanalen wijder open te zetten. Dit gebeurt door Noradrenaline
o Increasing heart rate: Noradrenaline (NA) → open sodium channels wider
- Snelheid van repolarisatie:
voor een lagere frequentie moet de daling sneller gaan door de kaliumkanalen wijder open
te zetten
o Decreasing heart rate: Acetylcholine (Ach) → opens potassium channels
Cardiomyocytes (hartspiercellen) only undergoes an action potential when a neighbouring
cardiomyocytes undergoes
Difference:
- Sodium entry is very quick, no pre-potential, quick rising potential. Open and close quick
- Slow rise in calcium
- Finally potassium channels open → repolarisation
, Cardiomyocytes have a very quick but long-lasting action potential
Calcium is important to induce contraction, Calcium concentration has to increase inside your cell
Excitation → sodium and calcium are entering inside your cell, but not enough, → calcium induced
calcium release = organel filled with calcium (sarcoplasmic reticulum calcium - SRCa) , calcium binds
and make this organel release about 10 times more calcium →calcium will bind to contractile
proteins → contraction of CMs
SRCa pumps calcium back into the organel (requires energy)
Contraction:
During rest myosin can’t bind to actin because there are other proteins that block it (tropomyosin) →
Calcium bind to .. complex shifts tropomysin → myosin can bind to actin → myosine kop buigt en
beweegt het actine (powerstroke) → hartspiercel spant aan
ATP is needed to release
Calcium is removed → binding stops
Conduction system
1. Start: sinoatrial (SA) node
2. AV node = delays the signal
3. AV bundle
4. Bundle branches
5. Purkinje fibres
