Neural interventions and cardiovascular disease- HYPERTENSION

Question 1

What are the 3 techniques for treating drug resistant hypertension ?

Answer 1

carotid sinus stimulation
renal nerve denervation
deep brain stimulation

Question 2

What is hypertension a major risk factor for ?

Answer 2

stroke, myocardial infarction, heart failure, kidney disease, peripheral vascular disease, cognitive decline and premature death

Question 3

What is the prevalence of hypertension at 45-54 years and? 75years?

Answer 3

as you get older the prevalence increases
45-54= men- 33% and women- 25%
>75 = men- 73% and women- 64%

Question 4

What is primary hypertension?

Answer 4

also known as essential hypertension
it is hypertension with an idiopathic cause
90%of people with hypertension have primary hypertension

Question 5

How many people worldwide are affected by hypertension ?

Answer 5

1 billion people - one of the biggest costs to the NHS

if it is left untreated it can lead to serious disease states

Question 6

Define hypertension:

Answer 6

BP has a skewed normal distribution within the population and the currently accepted model assumes risk is continuously related to BP

Question 7

What is stage 1 hypertension ?

Answer 7

in surgery, BP is >140/90mmHg or HBPM/ABPM is >135/85mmHg- these results indicate a potential risk of suffering hypertension
wouldn’t necessarily receive treatment but suggestions of changes in diet and exercise

Question 8

What is stage 2 hypertension ?

Answer 8

in surgery BP is >160/100mmHg or ABPM/HBPM is >150/95mmHg

- likely to be prescribed anti-hypertensive drugs

Question 9

What is stage 3 hypertension ?

Answer 9

in surgery BP is >180/110mmHg or higher

admit to hospital and administer treatment straight away because it is at a level that may cause organ damage

Question 10

How can you reduce vascular constriction ?

Answer 10

using calcium channel blockers- they block the influx of calcium ions induced by the sympathetic nerve releasing noradrenaline to bind to alpha-1 R which causes calcium channels to open

Question 11

Why are beta-blockers useful ?

Answer 11

they act upon the heart to reduce rate and strength of contraction - this helps to reduce BP

Question 12

What are the current treatments that act on the renin-angiotensin system ?

Answer 12

ACE inhibitors= they reduce the circulating levels of angiotensin 2 which prevents it activating the suprarenal gland causing the release of aldosterone which maintains fluid and sodium retention
it also prevents it acting on the NTS, CVLM causing central activation of sympathetic activity and furthermore it prevents it acting on the arterial walls and causing vasoconstriction

Question 13

Why do we need new therapies for hypertension ?

Answer 13

because a large number of patients dont respond to the current therapies

Question 14

What did a study demonstrate about the standard treatments?

Answer 14

found that if they gave the current standard treatments more aggressively from the start then it causes a greater decline in BP then if they are given at much lower doses

Question 15

What can you do to the basal tone of sympathetic control on blood vessels ?

Answer 15

if you decrease the basal tone then you can cause vasodilation causing smooth muscle to relax and subsequently reducing BP
if you increase the basal tone on the arterial walls you can enhance the vasoconstriction and therefore increase BP

thought that maybe essential hypertension is being caused by increased sympathetic activity

Question 16

How was human sympathetic nerve activity measured in leeds?

Answer 16

using the common peroneal nerve just behind the knee they inserted a recording electrode and then just below a reference electrode is inserted
the activity in this nerve is representative of sympathetic activity because the activity is going to smooth muscle but also skin which is a slight limitatoin of the process
record the action potentials in the nerve

Question 17

What was the difference in MSNA in different groups of patients with normotsive, stage 2 and 3 hypertension ?

Answer 17

normotensive group= about 40 bursts per 100bpm
stage 2 group= nearly 60 bursts per 100bpm
stage 3 group= nearly 70 bursts per 100bpm
there is a correlation between sympathetic nerve activity and increased BP - as BP increases, sympathetic nerve activity increases

Question 18

What was shown in the carotid sinus stimulation experiment in rabbits?

Answer 18

they cut their carotid sinus nerves and inserted an electrode to stimulate just that nerve
as they increase the stimulus intensity it caused a much greater drop in BP

Question 19

What did the dog model of carotid sinus stimulation show ?

Answer 19

the hypertensive dogs which had carotid sinus stimulation had the greatest drop in BP compared to all other control groups and this decrease was maintained

Question 20

What happened in the 60s when they carried out carotid sinus stimulation in humans?

Answer 20

a receiver was placed under the skin and then they put a transmitter on the skin to activate it, this caused stimulation of the leads around the carotid sinus
limitations of this treatment are that the battery pack will only last a couple of years and it caused quite a few side effects, with some people even dying
as it was in the 60s, the idea was good but unfortunately they didn’t have the technology to carry it out

Question 21

What is the rheos system ?

Answer 21

the electrodes are wrapped around the whole carotid sinus so the whole structure is stimulated
- causes stimulation of baroreceptors in carotid sinus to stimulate a decrease in BP

Question 22

What did the rheos system show?

Answer 22

once it is turned on you get a substantial decrease in BP and HR and sympathetic activity drops almost to zero
once you switch it off you get a sudden rise in BP and sympathetic activity

Question 23

What did a long term study of the rheos system show?

Answer 23

measuring the effects of this system on both SBP and DBP each year for 3 years demonstrated that the effects are maintained

Question 24

The rheos system stimulates the whole carotid sinus so what were they worried about and how did the test to see if these effects were present ?

Answer 24

if you are stimulating the whole carotid sinus you may also be activating chemoreceptors which will affect respiration and cause an increase in sympathetic activity and therefore the effects upon BP will be counteracted

took measures of respiration

• measured tidal co2 volume and didn’t see much of a change
• measure MAP at different frequencies and this demonstrated those at at higher voltages were more effective at reducing BP

Question 25

What was the idea behind renal nerve denervation ?

Answer 25

altering either efferent or afferent renal nerves may be able to reduce increased BP induce the the renin-angiotensin system

Question 26

What is the renal denervation procedure?

Answer 26

1) catheter inserted into femoral artery- pass tube up the femoral artery to the renal artery- invasive
at the end of the catheter is a frequency generator
2) advanced into renal artery which senses changes in BP
3) the radio frequency generator applies 4-6 low power radio frequency treatments along the length go both renal arteries- heats up and emits radio waves to destroy the nerves therefore reducing signalling between brain and kidney

Question 27

What did 1 month, 3 month and 6 month measures of the effects of renal denervation show?

Answer 27

at 1 month the BP had substantially declines compared to control group by 20 mmHg
at 3 months this decline was maintained at 24 mmHg
and at 6 months it had dropped by 32mmHg
results were promising that this process was effective
also did safety effects and these were promising

Question 28

Due to the success of the renal denervation study what was carried out next?

Answer 28

symplicity HTN-3 trial
in this study they used a fake procedure and double blinded trials
so the control group thought they had had the renal denervation but actually they hadn’t - gold standard control
the trial was stopped after 6 months as there was no difference in BP between the sham and test group

Question 29

Why could have the simplicity HTN-3 trial failed?

Answer 29

the number of nerve ablations performed on the test group was variable between patients- no standardised ablation - some had it done 4 times while others had it done 20 times, however those that had it done more times did seem to show more decline in BP
also 40% of patients in the trial changed their anti-hypertensive drugs during the study and therefore this is an unexpected confounding factor

Question 30

What are the possible mechanisms underlying renal denervation process?

Answer 30

a decrease in efferent renal sympathetic activity- causes an increase in renal blood flow and a decrease in renin and blood pressure
a decrease in afferent renal sympathetic activity- causes a decrease in central sympathetic nerve activation
also previous studies have shown a decrease in renal and whole body noradrenaline spillover and sympathetic nerve activity

Question 31

What was the decline in muscle sympathetic nerve activity in patients who had renal denervation ?

Answer 31

at the start they had 56 bursts/min
after 1 month they had 41 bursts/min
after 12 month they had 19 bursts/min

Question 32

Where do they stimulate in deep brain stimulation to treat hypertension ?

Answer 32

the PAG in the midbrain

this would not be a standard treatment because it is extremely invasive

Question 33

What did they observe by carrying out deep brain stimulation ?

Answer 33

when the dorsal PVG/PAG were stimulated there was a increase in SBP/DBP
when the ventral PVG/PAG were stimulated there was a decrease in SBP/DBP
stimulating different areas of the brain which are close association with each other causes very different effects

Question 34

What other parameters were affected by deep brain stimulation ?

Answer 34

• decrease in BP
• increase in blood flow due to vasodilation
• decrease in resistance
• increased co
• increased SV

Question 35

How might DBS work ?

Answer 35

stimulating the PAG could inhibit the activity of the RVLM to reduce sympathetic nerve output and therefore reduce BP
it could also involve the NTS which can act on the CVLM and then this can act on the RVLM