Neural interventions in heart failure

Question 1

What is the normal neural control of the heart?

Answer 1

heart is autorhythmic- therefore without any neural input the heart will continue to beat
intrinsic HR= 100bpm due to SAN
at rest, parasympathetic input decreases HR to 60-70bpm- slows the SAN activity
maximum HR= 220-age-
- as you age your max HR decreases as it cannot maintain as high a HR

Question 2

Which is the initial effect of heart failure?

Answer 2

it causes decreased cardiac output

Question 3

What happens in heart failure to attempt to improve cardiac output?

Answer 3

neurohumoral activation
- sympathetic system increases to increase vasoconstriction and HR
- renin-angiotensin system is activated to induce sodium and fluid retention
BUT both these effects actually adds further stress to the heart and increases damage therefore potentiating heart failure - progressive disorder

Question 4

What can cause heart failure?

Answer 4

myocardial infarction is the main cause of HF
- blockage of one of the coronary arteries causes part of the heart to die and once you’ve damaged cardiac muscle cells you cant replace them- they are replaced by fibrous scar tissue that is not contractile therefore reducing cardiac output

Question 5

What does it mean by a compensated heart and a decompensated heart ?

Answer 5

compensated heart= a heart that has undergone the neurohumoural changes causing hypertrophy- muscle cells enlarged as they are being told to work harder
decompensated heart= the extra work load induced by neurohumoural changes has caused heart cells to die and be replaced by fibrous tissue making it less contractile- its a floppy heart - thin walls and poor at contracting

Question 6

What is class 1 heart failure?

Answer 6

without limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitations to dyspnea - mild

Question 7

What is class 2 heart failure?

Answer 7

slight limitation of physical activity. They are comfortable at rest. ordinary physical activity causes fatigue, palpitations or dyspnea - difficulty breathing

Question 8

What is class 3 heart failure?

Answer 8

marked limitations of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, dyspnea or palpitations

Question 9

What is class 4 heart failure?

Answer 9

inability to carry out any physical activity without discomfort. Symptoms are present at rest or minimal exertion

Question 10

What are the current treatments?

Answer 10

Beta-blockers= propanolol- helps to mitigate the effects of the sympathetic nervous system - reduce HR
ACE inhibitors= reduce angiotensin 2 production, reduce it increase in BP both peripherally and centrally

Question 11

What is an indicator of autonomic function ?

Answer 11

heart rate variability
reliant on the fact the heart is not a metadrome
measure cardiovascular autonomic function

Question 12

What happens to HR when you are breathing?

Answer 12

when you breathe in your HR increases slightly whereas as you breathe out your HR decreases slightly

Question 13

What 2 things can be looked at by measuring the difference between R-R intervals?

Answer 13

TIME-DOMAIN= looking at statistical analyses
FREQUENCY DOMAIN= spectral methods to look at oscillation
it provides a measure of the contraction of the ventricles

Question 14

What are the important peaks in a power spectrum?

Answer 14

HF peak= beat to beat changes in HR controlled by parasympathetic nerve- fast chnages in HR
LF peak= controlled by both parasympathetic and sympathetic nervous system - slower changes in HR
look at the ratio between these peaks to get a balance of autonomic balance - low = higher parasympathetic activity
high- low parasympathetic activity

Question 15

What is microneurography?

Answer 15

recording muscle sympathetic nerve activity
- insert electrode into tibular nerve and record the actions potentials upon vasoconstrictor axons
very direct measure

Question 16

When sympathetic activity is stimulated what is shown in microneurography?

Answer 16

increased HR and BP

if you’ve recorded from 1 axon then all the action potentials recorded should overlap perfectly to give you one trace

Question 17

What should be indicated about baroreflex sensitivity when systolic BP is plotted against R-R interval?

Answer 17

as BP increases you should get a decrease in HR and therefore an increase in R-R interval producing a pstitive linear line
BUT if the graph is a horizontal line it indicates that as BP increases the R-R isn’t increasing and so the HR isn’t slowing so there is very little vagal input

Question 18

With normal baroreflex sensitivity what should be shown about R-R interval ?

Answer 18

normal baroreceptor sensitvity should correlate with increase of 3ms in R-R for every 1mmHg increase in BP

Question 19

With impaired baroreflex activity what is shown about the R-R interval?

Answer 19

low levels of parasympathetic activity indicated by a change in R-R interval of

Question 20

What is characterised of HF?

Answer 20

sympathetic activation and parasympathetic withdrawal

Question 21

What happens to % change in HR when propanolol is given to normal and HF people?

Answer 21

HR is decreased in both groups, slightly more in HF but not much
- sympathetic activity is reduced in both groups by relatively similar amounts

Question 22

What happens to the % change HR when propranolol and atropine are given to normal and HF people?

Answer 22

normal group have a substanially higher HR but HF group doesn’t increase nearly as much
- this indicates that their parasympathetic activity was low to begin with, therefore blocking with atropine hasn’t made much of a difference

Question 23

What happens to baroreflex sensitivity when propranolol is given ?

Answer 23

in normal group they become slightly less sensitive and the HF group become slightly more sensitive but it doesn’t appear to make a huge difference

Question 24

What happens to baroreflex sensitivity when atropine and propranolol are both given ?

Question 25

From the experiments with atropine what is indicated?

Answer 25

promoting parasympathetic activity may help to improve autonomic function

Question 26

What is carotid sinus stimulation?

Answer 26

place electrodes around the carotid sinus in the neck
stimulator implanted under chest wall
increases sympathetic activity
electrically stimulating carotid sinus increases BP- artificially stimulating baroreceptor reflex artificially stimulates parasympathetic activity

Question 27

What has carotid sinus stimulation shown to improve ?

Answer 27

improves left ventricular function

Question 28

What did a canine model using carotid sinus stimulation show?

Answer 28

canine heart failure model was induced by coronary artery microembolisation - mimics myocardial infarction

• after 3 months haemodynamics were measured and demonstrated improvements
• improved cardiac output
• improved left ventricular fraction output
• huge decrease in plasma noradrenaline levels

Question 29

With the canine model of heart failure what indicates that the model may not have been the best ?

Answer 29

the models which didn’t receive carotid sinus stimulation didn’t demonstrated decreased CO

Question 30

What other beneficial effect was demonstrated by baroreflex stimulation ?

Answer 30

attenuated left ventricular remodelling
- less fibrosis and enlargements in the cardiomyocytes and the capillaries were closer to cardiomyocytes in the carotid sinus stimulated model

Question 31

What are the acute and chronic effects of baroreflex stimulation in patients?

Answer 31

acute- decreases BP and decreases sympathetic nerve activity so less vasoconstriction
chronic- decreases left ventricular mass after 12 months, this was surprising because remodelling go the heart was thought to be irreversible

Question 32

What are some limitations of vagal nerve stimulation ?

Answer 32

invasive and expensive

- orginally developed for epilepsy

Question 33

What % of the cervical vagus nerve are afferent and efferent fibres?

Answer 33

afferent= 80%- send info into CNS to alter central autonomic control 
efferent= 20% - alter efferent fibre activity

Question 34

What is the principal of vagal nerve stimulation ?

Answer 34

by activating nerves in the neck the afferent fibres are activated which could alter central autonomic control or it could activate efferent fibres to target organs directly to enhance parasympathetic activity

Question 35

What happened in a study of vagal nerve stimulation in rats?

Answer 35

heart failure model induced by coronary artery ligation- did cause 60% mortality
1 week later an implant vagus stimulator and telemetry device was implanted to record HR and BP
1 week after that VNS treatment started and lasts for 6 weeks
VS group of rats had smaller hearts so less enlargement occurred, reduced plasma noradrenaline so less sympathetic activity and reduced release of BNP( released from the heart when its stretched)
vs group had much better survival rates - 90% survival compared to 50% in control group

Question 36

What was the canine model for vagal nerve stimulation and what occurred?

Answer 36

model was induced by an inserted pacemaker which drives heart at very high rate to induce hf
then they stimulated the right cervical vagal nerve in 8 dogs and 7 were untreated
the vs group had much higher parasympathetic activity
markers of inflammation, sympathetic activity and RAAS activity were all reduced
- reduced neurohumoural effects to reduce progression of hf

Question 37

In a clinical trial of vagus nerve stimulation what happened?

Answer 37

improvements in quality of life measurements - improved the distance in which they could walk at both 3 months and 6 months and they felt better and much happier
they also showed improvements in heart rate variability at both 3 months and 6 months and this indicates there is more parasympathetic activity- its an indirect measure

Question 38

From the clinical trial of VNS what was shown in the the new york heart association classes?

Answer 38

• no longer any patient with class 4
• of the 15 that had class 2, by 6 months 10 of them were classified as class 1
  symptoms substantially improved

Question 39

What are the limitations of VNS?

Answer 39

cough, neck pain and can affect your voice- horse voice

its invasive so if you are unwell you will not be able to undergo treatment

Question 40

What was the next idea for VNS ?

Answer 40

to try and activate the vagus nerve by cutaneous stimulation
the auricular branch of the vagus nerve is able to be stimulated by stimulating the ear

Question 41

What happened when the auricular nerve was stimulated by electrical acupuncture?

Answer 41

10 days later there were drastic improvements
there was no need for vasodilators and there was no pain at rest
significant improvements in
- spontaneous recovery of cardiac sinus rhythm
- cardiac insufficiency
- stable haemodynamics, sinus rhythm

Question 42

What is tVNS?

Answer 42

transcutaneous vagus nerve stimulation
clipped stimulator onto tragus to stimulate auricular branch of vagus- this was tested in healthy individuals
acute stimulation of 15 mins of 200microsecond pulse frequency at 30Hz demonstrated beneficial effects- there was a significant decrease in LF/HF ratio demonstrating the promotion of parasympathetic activity- improved heart rate variability
also significantly reduced sympathetic vasoconstrictor activity

Question 43

What is the theoretical pathway of the auricular branch ?

Answer 43

its known to project to the NTS
So maybe it projects to NTS to reach brainstem to increase parasympathetic outputs
such that NTS projects to DMN or maybe to the CVLM to inhibit RVLM to decrease sympathetic output