Lecture 16 - Control Of The Heart Rate • Physiology And Pharmacology Flashcards
How does the heart set its own rate
By the depolarisation rate of the sinoatrial node
What is the heart innervated by
Both divisions of the autonomic nervous system
What does increased activity in the sympathetic nervous system cause on the heart
An increase in heart rate
What is tachycardia
An increase in heart rate
What effect does an increase in the activity of the parasympathetic nervous system have on the heart
It causes a decrease in heart rate
What is bradycardia
A decrease in heart rate
How do the two divisions of the autonomic nervous system effect the heart rate
By changing the slope of the pacemaker potential
What are changes in the heart rate known as
Chronotropic effects
What is vagal tone
An internal biological process referring to the activity of the vagus nerve
What are the parasympathetic and sympathetic effects on the heart
Antagonistic
What is heart rate determined by
The balance between the inhibition and stimulation of the SA node
What inhibits the SA node
The vagus nerve
What stimulates the SA node
The sympathetic nerves
What division dominates the heart under rest conditions
Parasympathetic division
What is activity of the autonomic nervous system coordinated by
The cardiovascular control centre
Where is the cardiovascular control centre located
In the brain stem
What neurotransmitter does the parasympathetic system release
Acetylcholine
What neurotransmitter does the sympathetic nervous system release
Noradrenaline
How do both division of the autonomic nervous system bring about their effects on the heart
By alternating the activity of the cAMP 2nd messenger pathway in innervated cardiac cells
What type of G-protien is ACh coupled with
Inhibitory G-protein
What effect does ACh coupled with its G-protein have on the heart
It reduces the activity of the cAMP pathway
What type of G-protein is NorAd couple with
A stimulators G-protein
What effect does NorAd coupled with its G-protein have on the heart
It accelerates the cAMP pathway
What is the primary means by which the heart rate is regulated
Autonomic innervation
What hormone also plays an important role in the regulation of heart rate
Adrenaline
What is adrenaline released in response to
Sympathetic stimulation
What effects do adrenaline and noradrenaline have on the heart
They increase the heart rate and force of myocardial contraction
What is another name for adrenaline
Epinephrine
What is another name for noradrenaline
Norepinephrine
What type of action is the changing of heart rate
Chronotropic action
What type of action is the change in force of myocardial contraction
Intropic action
How does adrenaline execute its affect on the heart
By reinforcing the direct effect of the sympathetic nervous system
How does the parasympathetic system decrease the heart rate
It causes hyperpolarisation of the SA node membrane and it decreases the rate of spontaneous depolarisation
What does hyperpolaristaion of the SA node membrane mean
It takes longer to reach threshold
What effect does ACh of K+ permeability
It increases it
How does ACh increase K+ permeability
By G-protein coupled inwardly-rectifying potassium channels
What are GIRKS
G-protein coupled inwardly-rectifying potassium channels
What effect does the parasympathetic system have on the AV node
It decreases the AV node’s excitability which prolongs transmission of impulses to the ventricles
What effect does the parasympathetic system have on the AP
It shortens the plateau phase of the AP in atrial contractile cells, weakening atrial contraction
Why is the AV nodal delay needed
So the atrial cells can contract before the ventricles
What does a shortened AP cause
Less calcium is able to enter the cell so the contraction is weakened
What effect does parasympathetic stimulation have on ventricular contraction
It has very little effect
What is the main effect of the sympathetic system to speed up the heart rate
It speeds up depolarisation so threshold is reached more rapidly
What does sympathetic stimulation of the AV node cause
It reduces the AV nodal delay
How does sympathetic stimulation reduced the AV nodal delay
By increasing conduction velocity
What effects does the sympathetic stimulation cause on the heart to increase heart rate
It speeds up the AP throughout the specialised conduction pathway, increases the contractile strength of atrial and ventricular contraction, it increases Ca2+ permeability and speeds up relaxation
How does the sympathetic system increase Ca2+ permeability
Through prolonged opening of the L-type Ca2+ channels
What is the pacemaker potential regulated by
The funny current
What is the funny current
A depolarising current
What is the funny current mediated by
Channels that are activated by hyperpolarisation and cyclic AMP channels
What are the cyclic AMP channels known as
Hyperpolarisation-activated cyclic nucleotide gated (HCN) channels
When hyperpolarisation happens after an AP what occurs
The activation of HCN channels in the SA node causing a slow depolarisation
Blocking the HCN channels causes
A decrease in the slope of the pacemaker potential and reduces the heart rate
What is ivabradine
A selective blocker of HCN channels
What is ivabradine used for
To slow the heart rate in patients with angina
Why is a slower heart rate favourable in angina
As it reduces the oxygen consumption
What does B1-adrenoceptors activation cause
An increase in the pumping of Ca2+, an increase in the rate of relaxation and an increased sensitivity to Ca2+
What effect does the activation of B1-adrenoceptors have on the heart
They enhance contractility
B1-adrenoceptors increase
Force, rate, cardiac output and oxygen consumption of the heart
B1-adrenoceptors decrease
Cardiac efficiency
What does a decrease in cardiac efficiency mean
The oxygen consumption is increased more than the cardiac work
What can B1-adrenoceptors cause disturbances in
The cardiac rhythm
What is a disturbance in the cardiac rhythm known as
An arrhythmia
What is adrenaline used in the treatment of
Cardiac arrest, emergency treatment of asthma and anaphylactic shock
What are the clinical uses of dobutamine
Acute, but potentially reversible, heart failure
What effect do B-adrenoceptor blockers have at rest
Little effect
What effect do B-adrenoceptor blockers have during exercise or stress
The rate, force and cardiac output are significantly depressed so there is a reduction in the maximal exercise tolerance
What effect do B-adrenoceptor blockers have on coronary vessel diameter
It is marginally reduced
What does the effect of B-adrenoceptor blockers mean for the heart
The myocardial oxygen requirements fall so there is better oxygenation of the myocardium
What are selective B1 blockers
Metoprolol and atenolol
Why do metoprolol and atenolol have an advantage
As B2-adrenoceptors are not affected much by them
What are the clinical uses of B-adrenoceptors
Treatment of disturbances of cardiac rhythm, hypertension, angina and heart failure
What is associated with a dysthymia
Excessive sympathetic activity associated with stress or disease
What can a dysthymia lead to
Tachycardia or spontaneous activation of latent cardiac pacemakers’ outside nodal tissue
What do B-blockers do
Decrease excessive sympathetic drive and help restore normal sinus rhythm
What is atropine
A non-selective muscarinic receptor antagonist
What does atropine cause
A moderate increase in heart rate
What does atropine have no effect on and why
Arterial blood pressure resistance as the resistance vessels lack parasympathetic innervation
What are the clinical uses of atropine
Reverse bradycardia following an MI, an adjunction to anaesthesia and in anticholinesterase poisoning to reduce parasympathetic activity
What is digoxin
A cardiac glycoside
What is the function of digoxin
It increases contractility of the heart
What is heart failure
When the cardiac output is insufficient to provide adequate tissue perfusion
What effect does heart failure have on the ventricular function curve
It is depressed
Examples of inotropic drugs
Digoxin and dobutamine
What do inotropic drugs do
Enhance contractility
Mechanism of digoxin
It binds to the a-subunit of the Na+/K+ ATPase and is in competition with K+
What can dangerously enhance the effects of digoxin
Low plasma K+ concentration (hypokalaemia)
What are the direct actions of digoxin
It shortens the AP and the refractory period in atrial and ventricular myocytes
What are the indirect actions of digoxin
Increased vagal activity, decreasing of the SA node discharge and decreasing the AV node conduction which increases the refractory period
What can a toxic dose of digoxin cause
Membrane depolarisation and oscillatory afterpotentials
