Saturday, June 9, 2012

Vagal nerve and vagal maneuvers

Vagal nerve is the main inhibitory nerve for heart and lungs in vertebrates. It reacts to stretching in internal organs (stomach and lungs) or blood vessels (during diving or high blood pressure). For example during deep inhalation vagal nerve causes slowed pulse. During diving this nerve shows it's more extreme ability to slow down heart rate, metabolism and oxygen use speed.
In diving seals reduction in pulse could be 80% and humans could reduce their heart rate up to ~50%. This effect is less obvious with longer breath holding because accumulating CO2 causes panicky feeling of suffocation with faster pulse.
Cutting vagal nerves remove this slowing effect from deep inhaling.
Vagal reflexes constrict upper airways causing coughing and breathing difficulties due to narrower throat and lung airways.

Vagal maneuver means almost any activity that activates vagal nerve (guidelines and warnings about their use for paramedics):
Medics may ask patients with too fast heart or too high blood pressure to inhale deeply, hold it in 5 seconds and slowly exhale through straw. In extreme cases it may cause fainting because in some people heart can stop for over 5 seconds with that sort of breathing. If that doesn't work they may try massaging carotid sinus on the side of neck but doctors often check for clogs because massaging blood vessels can release debris that can block blood vessels and possibly kill. Other safer ways to activate vagal reflexes is to but face in cold (below 21 C) water or add pressure to eyes.
Guidelines asked to immediately stop vagal maneuvers when pulse falls below 100 beats per minute.

Vagal nerve on above image is marked with X (vagal nerve is 10th cranial nerve). It exits brainstem in medulla and unlike other nerves it doesn't pass spine so spinal damage rarely damages vagal nerve. All internal organs along with upper airways are connected to vagal nerve.

Vagal nerve uses acetylcholine and if that is blocked then vagal maneuvers don't work. For example muscarinic acetylcholine antagonists like atropine or scopolamine can cause life threateningly fast heart rate because in sober people it usually works constantly to keep heart speed slowed.   

In case people get new heart they lose nerve connections with heart. That causes almost constantly fast heart rate and heart doesn't react to vagal maneuvers until vagal nerve grows back to heart but even then it's weaker than before surgery. Heart disease can also reduce connections between heart and vagal nerve causing increasingly faster pulse in people who have poor heart or possibly some local damage there.

In case you wondered how transplanted heart keeps beating- it doesn't need nervous system for that. Adrenaline and noradrenaline from adrenal glands reach heart through blood and activate its muscles. Healthy people have some stimulating nerve connections to heart so their pulse reacts within second to increased physical stress but in people with heart transplant (or with damaged heart) pulse may take a minute to react to new activity level.

Comparison of vagal maneuver effects in younger people. (table of results).
Largest pulse reduction (43%) happened when sitting people put their faces in cold water.
Deep inhaling and forced exhaling caused 25% drop in heart rate.
Neck massaging reduced pulse by 17%.
Pressure on eyes reduced pulse by ~11-19%.

Vagal maneuvers can cause short asystole (heart flatlining). 23 patients who were known to faint during vagal maneuvers got device that recorded how often and for how long their heart stopped. Measuring lasted 15+/-7 months with average age 64+/-12 years. 17 patients (74%) had at least 1 over 3 second asystole in that period. Asystoles lasting 3-6 seconds were measured in 14 patients and in total these events happened 1765 times causing fainting 12 times (0,7%). In 47 cases 11 different patients had asystoles lasting over 6 seconds and that caused fainting 20 times (43%).
Asystoles were mostly symptomless.  
Study on seal vagal reflex. When they dived on their own will then their pulse slowed by about 80% (from about 150 bpm to 30-50 bpm). Several drugs were tested on that reflex (graph). Blocking adrenaline receptors (alfa and beta blocker on graph) didn't seem to affect it much but when they blocked muscarinic acetylcholine receptors that vagal nerve uses for inhibition then vagal reflex almost disappeared (maybe 10% reduction in pulse during diving). Like in humans seals also experience reduction in pulse even if they just put only their face under cold water.
No matter what drugs were tested seals seemed to stay under water same amount of time.
Possible trigger for reduced pulse might have been blood pressure near skin because seals outside water had same reduction in pulse if they were injected with phenylephrine. Phenylephrine is alfa adrenaline receptor agonist that increases arterial blood pressure by constricting tiny vessels near skin. In seals injection of phenylephrine could lower their pulse from 150 beats per minute to less than 30 bpm but this effect was almost nonexistent if seals were given muscarinic acetylcholine antagonists so their vagal nerve wouldn't work.

Vagal nerve stimulation (VNS) is electric stimulation of vagal nerve to get some benefit (from activated vagal nerve). It was originally tried against epilepsy in hopes of getting rid over excess brain activity and later it was used more against depression although usefulness of this is not clear. Electric stimulation usually lasted 30 seconds at time every 5 minutes and battery could last 10 years. Because vagal nerve also controls muscles then many side effects of VNS happen near neck.
Common side effects are coughing, change in voice, difficulty swallowing, breathing difficulties (especially during physical activity), throat pain, neck pain and discomfort in area with implant. Often people switch them off (by putting magnet they get with implant on implanted area) to get some exercise.   

In one case VNS patient under general anesthesia got breathing difficulties every 5 minutes when his VNS implant started working but stronger air pressure was enough to overcome this problem.

VNS uses 20-30 Hz frequency and uses current of 1-2 milliamperes. Operation has ~1% risk of infection and sometimes damage to vagal nerve. Common side effects are pain in head, throat, jaw, teeth or neck. 
Authors checked how good it may be against depression and they didn't find clear benefits from VNS against depression.

By year 2000 over 6000 people had got VNS implant against epilepsy. It was discovered around 1950s that VNS stopped epilepsy in dogs and caused slow synchronous brain waves (common in sleepy or calm states) in frontal lobes and amygdala. About 30 years later it was tried on humans against epilepsy and it seems to be beneficial for that purpose.
In addition to brain inhibition during VNS researchers also noticed a weaker inhibitory phase that lasted ~4 times longer than vagal stimulation.
Brain inhibition may happen through NTS (nucleus tractus solitarius) that gets all sensory vagal signals. NTS controls reticular formation and LC (locus coeruleus) which both have stimulating roles. Damaging LC removed anti-epileptic effects of VNS. 
Sometimes right side is preferred for VNS because on left side it could influence heart too much but if implant is low enough then i may have no direct effect on heart because part of vagal nerve that slows heart branches out of main vagal nerve around neck area. 
In a study with 313 VNS patients VNS seemed to reduce epilepsy rate by 25-30% compared to placebo group.

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