Heart failure and Therapy
Annemarijn Koops
College 1: fysiology of the cardiovasculair system
Function of the heart:
1. Pumps oxygen-poor blood to the lungs
2. Pumps oxygen-rich blood to all organs in the body.
3. Together with blood vessels, ensures sufficient perfusion of all organs and tissues.
4. Contraction and relaxation of the heart determine the cardiac output, which is
managed through the coordination of approximately 2-3 billion cardiomyocytes.
Excitation-contraction coupling refers to the
contraction of the heart after the electrical
stimulation of cardiomyocytes.
The heart can beat independently without neural
or hormonal input. It is able to maintain its own
rhythm without relying on hormones or the
nervous system.
The heart beats autonomously due to pacemaker
cells. These cells are spontaneously active,
generating electrical impulses without external
stimuli. Pacemaker cells are located in specific
areas such as the SA node and AV node.
SA node is the heart's natural pacemaker, generating spontaneous electrical impulses (
starting signal).
AV node acts as a "bridge" that delays the impulse before sending it to the ventricles, giving
the atria enough time to fully pump blood into the ventricles.
AV bundle (bundle of His) divides the impulse into two branches, directing it to the left and
right ventricles.
Purkinje fibers then distribute the electrical impulse across the walls of the ventricles,
ensuring an effective contraction.
Pacemaker cells
Sodium (Na⁺) flows in first, and when a threshold of -40 mV is reached, calcium (Ca²⁺) also
enters, causing a peak in the action potential. Eventually, potassium (K⁺) flows out, bringing
the membrane potential back to the starting point.
,Action potential
1. Rapid depolarization (Na+ erin, fast)
2. Plateau (Ca 2+ erin, slow)
3. Repolarization (K+ eruit, slow)
An action potential is the electrical change that
occurs in the heart during a heartbeat.
ARP = No new action potential can be initiated,
regardless of the strength of the stimulus. Crucial to
prevent the heart from contracting too rapidly in
succession.
RRP = A new action potential can be initiated, but
only with a stronger-than-normal stimulus.
SP = The heart is extra sensitive to stimuli, and an
action potential can be triggered with a weaker
stimulus.
During exercise, blood flow increases in the skeletal muscles, heart, and skin. Blood flow
decreases in the kidneys and abdominal viscera, while it remains constant in the brain.
Parasympathetic nervous system influences the heart via the vagus nerves. Acetylcholine
binds to the M-receptor, lowering heart rate and reducing contractile strength (less activity),
causing hyperpolarization.
Sympathetic nervous system acts via the thoracic spinal nerves. (Nor)epinephrine binds to
the beta-receptor, increasing both contractile strength and heart rate (more activity), leading
to reduced repolarization.
Heart rate is determined by:
- Resting membrane potential of the SA node: The less negative this resting membrane
potential is, the faster the cell can reach the threshold. (The less negative, the faster).
- Speed (velocity) of depolarization: The steeper the slope, the faster the cell reaches the
threshold to start a new action potential. (The steeper, the faster).
To prevent the heart from continuing to contract during transplantation from donor to
recipient, the heart is placed in a special solution called cardioplegic solution. This solution
contains a high concentration of potassium, which lowers the resting membrane potential,
preventing the cells from repolarizing. No new action potential can be generated, protecting
the heart from ischemia (lack of oxygen) and damage.
During an action potential, Ca2+ can enter
the cell through L-type calcium channels. It
then passes through the ryanodine
receptor (RyR), leading to further Ca2+
release from the sarcoplasmic reticulum
(SR) (specialized storage site for Ca2+).
This process is known as calcium-induced
calcium release (CICR).
,The released Ca2+ from the SR binds troponin, a protein on actin filaments, triggers muscle
contraction. After the contraction, the Ca2+ needs to be removed from the cell, done through
the SERCA pump. This pumps Ca2+ back in SR, where it is stored for the next heartbeat.
In addition, the Na+/K+-ATPase helps restore ion balance by removing excess sodium from
the cell. This exchanges 3 Na+ ions out of the cell for 2 K+ ions into the cell using ATP.
CICR is crucial for heart function, ensuring that a small initiating signal (Ca2+ influx via
L-channels) leads to a larger release of Ca2+, necessary for the strong contraction of the
heart muscle.
L-type calcium antagonists (verapamil or diltiazem) block the Ca2+ channels. This prevents
Ca2+ from entering the cell, resulting in a lower heart rate, reduced electrical impulses
(decreased conduction through the AV node), and weaker heart muscle contractions.
Phases cardiac cycle:
1. Atrial kick: Blood flows from atria to ventricles. The
AV valves are open, and the semilunar (aortic and
pulmonary) valves are closed.
2. Isovolumetric contraction: ventricles begin to
contract, but the pressure is not yet high enough.
Both the AV and semilunar valves remain closed.
3. Ejection: Once the pressure is high enough, the
semilunar valves open, and blood is ejected to the
lungs and body. The AV valves remain closed.
4. Isovolumetric relaxation: After the ejection phase,
the ventricles relax, but the pressure is still low. Both
the AV and semilunar valves are closed.
5. Passive filling: Once there is enough pressure, the
AV valves open, and blood flows passively into the
ventricles. The semilunar valves remain closed.
Filling → Isovolumetric contraction (ventrikels)→ Ejection → Isovolumetric relaxation
(ventrikels ontspannen) → Filling (and the cycle repeats).
"Blood flow through the heart is completely determined by pressure differences."
LA = Left atrium: Pressure stays
relatively low but increases during phase
1 (filling).
LV = Left ventricle: Pressure rises
significantly during phases 2 and 3
(contraction and ejection).
Aorta: remains high in pressure due to
the elasticity walls, helps maintain blood
pressure.
, Stroke volume (SV) = End Diastolic Volume (EDV) – End Systolic Volume (ESV).
Example: EDV (120) - ESV (40) = SV = 80 ml/beat.
SV = the amount of blood ejected from the ventricle with each cardiac cycle.
Ejectiefraction = (EDV - ESV) / EDV
Example. (120 - 40) / 120 = 67%
With heart failure this percentage is < 45% (systolic dysfunction).
Valves: Tricuspid (Right) en Mitral (Left).
Difference LV and RV
Heart rate is influenced by the CNS, the sympathetic effects on the SA node, and hormones
such as (nor)epinephrine and thyroid hormones.
Stroke volume is affected by end-diastolic volume (preload), sympathetic contractility
(via norepinephrine), and peripheral adjustments (afterload).
Frank-Starling mechanism
Allows the heart to automatically adjust stroke volume in response to changes in venous
return. This ensures efficiency and balance in the heart’s functioning, supporting increased
demands during physical activity and preventing potential complications like heart failure. It
is essential for adapting heart function to the body's changing needs.
Adrenergic stimulation
(nor)epinephrine and acetylcholine activate PKA (protein kinase A), speeding up the
SERCA pump, which leads to faster reuptake of Ca²⁺ into the sarcoplasmic reticulum
(SR). This speeds up the heart muscle's relaxation and increases the Ca²⁺ release from the
SR. Additionally, it reduces the calcium sensitivity of the myofilaments, allowing for faster
relaxation, making the heart more efficient and responsive.
Afterload is the pressure on the AP-valves needed to push blood to the body and lungs.
When afterload increases and is high (vasoconstriction ↑ and vasodilation ↓) it becomes
harder to maintain an adequate stroke volume. Key factor contributing to heart diseases.
Prolonged high demand for blood - during intense physical exercise, pregnancy, or
myocardial infarction - can lead to hypertrophy of the heart muscle.
