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State of the art paper
Corresponding author:
Dr Tumul Chowdhury MD, DM
Department of Anesthesia
and Perioperative Medicine
2
nd
Floor, Herry Medovy House
671-William’s Ave
Health Sciences Center
University of Manitoba
Winnipeg, Canada R3E 0Z2
Phone: (204) 298 5912
Fax: (204) 787 4291
E-mail:
tumulthunder@gmail.com
1
Faculty of Sports Sciences, University of Rouen, Mont-Saint-Aignan, France
2
Department of Anesthesia and Perioperative Medicine, University of Manitoba,
Winnipeg, Canada
3
Department of Neurosurgery, University Hospital Paris, Paris, France
Submitted: 19 March 2013
Accepted: 30 June 2013
Arch Med Sci 2015; 11, 2: 419–426
DOI: 10.5114/aoms.2015.50974
Copyright © 2015 Termedia & Banach
The trigeminocardiac reflex – acomparison with
the diving reflex in humans
Frederic Lemaitre
1
, Tumul Chowdhury
2
, Bernhard Schaller
3
Abstract
The trigeminocardiac reflex (TCR) has previously been described in the
literature as a reflexive response of bradycardia, hypotension, and gas-
tric hypermotility seen upon mechanical stimulation in the distribution of
the trigeminal nerve. The diving reflex (DR) in humans is characterized by
breath-holding, slowing of the heart rate, reduction of limb blood flow and
agradual rise in the mean arterial blood pressure. Although the two reflexes
share many similarities, their relationship and especially their functional
purpose in humans have yet to be fully elucidated. In the present review, we
have tried to integrate and elaborate these two phenomena into aunified
physiological concept. Assuming that the TCR and the DR are closely linked
functionally and phylogenetically, we have also highlighted the significance
of these reflexes in humans.
Key words: reflexes, oxygen-conserving effects, breath-hold, brain,
trigeminocardiac reflex, diving reflex.
Introduction
The trigeminal cardiac reflex (TCR) and diving reflex (DR) are neuro-
genic reflexes that share many similarities in their clinical presentations
and mechanisms of action; however, their relationship and especial-
ly their functional purpose in humans have yet to be fully elucidated
[1–10]. In the present review, we have tried to integrate and elaborate
these two phenomena into aunified physiological concept. We have also
highlighted the significance and current role of these reflexes in humans.
Definitions
The trigeminocardiac reflex
The TCR is awell-established neurogenic reflex which manifests as
bradycardia, hypotension, and gastric hypermotility seen upon mechan-
ical stimulation in the distribution of the trigeminal nerve [1–3]. Initial
reports were based on animal experiments; however, TCR in neurosurgi-
cal patients was first elaborated by Schaller et al. in 1999 [3–6]. In their
key work, Schaller et al. meticulously defined TCR, and their observa-
tions are still used and commonly appreciated by researchers worldwide
Frederic Lemaitre, Tumul Chowdhury, Bernhard Schaller
420 Arch Med Sci 2, April / 2015
[1–3, 5–7]. The incidence of the TCR in neurosur-
gical procedures involving or near the trigeminal
nerve vicinity was reported to be about 10–18%
[7, 8]. These studies have usually taken a 20%
decrease in hemodynamic changes as the cut-off
limit to define TCR; therefore the true incidence
may be even higher. Moreover, the intensity of TCR
is also afactor of the intensity of stimuli like the
DR, which increases proportionally to decreasing
water temperature [1–8]. At the molecular level,
TCR is believed to be aphysiological oxygen con-
serving reflex which when incited initiates apow-
erful sympathetic system response (within afew
seconds) and thus increases the cerebral blood
flow (CBF). This regional elevation of CBF without
accompanying changes in the cerebral metabolic
rate of oxygen or glucose rapidly provides oxygen
to the brain in amore efficient manner. External
stimuli and individual factors have avariable influ-
ence on inciting the TCR in humans [8].
The diving reflex
The diving reflex in humans is characterized
by breath-holding, slowing of the heart rate, ade-
crease in cardiac output with sympathetic mediat-
ed peripheral vasoconstriction, an increase in mean
arterial blood pressure (MABP) and splenic contrac-
tion [9–16]. Blood is re-directed to more vital or-
gans (heart, brain and lung) while at the peripheral
level poor irrigation of tissues manifests as lactate
accumulation. A simultaneous splenic contraction
is also observed which indeed increases the stat-
ic apnea duration and helps in further resurgence
of red blood cells in the blood circulation [17, 18].
These phenomena also exist during repeated epi-
sodes of dynamic apnea [13]. Diving reflex is firstly
triggered by breath-holding and is augmented fur-
ther by immersion of the face into cold water [19,
20]. This response is also very prompt; therefore,
it can be considered as areflex. The inhibition of
the respiratory centers and the absence of afferent
input from pulmonary stretch receptors increase
vasomotor and cardio-inhibitory activity [21–23].
All these modifications allow economizing of the
oxygen stores for the breath-hold diver (BHD) [18,
21, 24–27]. Similar to the TCR, the DR also acts as
a protective oxygen-conserving reflex (OCR) and
aims to keep the body alive during cold water im-
mersion. Thus it protects the vital organs (the heart
and the brain) from extreme hypoxia. The DR in hu-
mans is modifiable by various factors including wa-
ter temperature, exercise, partial pressure of arte-
rial oxygen (PaO
2
), carbon dioxide tension (PaCO
2
)
and psychological factors [22].
Though the two reflexes share alot of similar-
ities, their relationship and especially their func-
tional purpose in humans have not yet been fully
elucidated. In the present article, we have tried to
elaborate the similarities as well as dissimilarities
between these two unique reflexes and therefore
possibly integrate these into one common mecha-
nism. We assume that partially, if not substantial-
ly, the TCR and the DR are closely linked function-
ally as well as phylogenetically and represent old
reflexes that are physiological in humans in the
first few months of life.
General similarities
There are obvious strong links between the
TCR and the DR that are generally accepted. Both
reflexes are based on the integrity of the trigem-
inal-brain stem reflex arc [2, 3]. In both, brady-
cardia is acommon manifestation and is induced
via reflex centers located in the medulla oblon-
gata [1, 28]. Efferent parasympathetic pathways
mediate bradycardia and similarly efferent sym-
pathetic pathways mediate peripheral vasocon-
striction.
General differences
The TCR occurs due to either peripheral or cen-
tral stimulation [3]. Stimulation of the trigeminal
nerve anywhere along the face including the nose,
orbit, eyeball and scalp (the area supplied by the
trigeminal nerve) up to the gasserian ganglion
(entry into the intracranial compartment) is con-
sidered as aperipheral TCR. The DR can be consid-
ered as aperipheral TCR. The gasserian ganglion
to the brainstem constitutes the rest of the tri-
geminal nerve course, and stimulation along this
part is considered as the central TCR. Peripheral
TCR stimulation may present with bradycardia
with or without hypotension, whereas central TCR
stimulation is usually followed by severe bradycar-
dia/asystole and hypotension [3, 8]. What differs
is that in the TCR there is asecondary decrease
in MABP, whereas in the DR the MABP gradually
increases. The difference might simply reflect the
fact that the stimulus in the DR is not ceased as
immediately as in the TCR. At present it is still not
clear whether this increase in MABP is specific for
all peripheral TCRs or only for asubgroup.
Bradycardia
It is awell-established fact that during breath-
hold diving, the heart rate (HR) becomes slower.
The reduction in HR is brought about by the in-
volvement of both central inspiratory and phasic
pulmonary afferent mechanisms [29]. Similarly,
it has been reported that tracheal intubation im-
posed during surgical procedures may give some
protection against activation of the TCR [30]. Ba-
bies under 6 months of age are excellent swim-
mers due to their DR: ababy’s air passage blocks
in contact with water, which explains the common
The trigeminocardiac reflex – acomparison with the diving reflex in humans
Arch Med Sci 2, April / 2015 421
observation of babies “swimming” under water
with open mouths.
Both reflexes, the TCR and the DR, have awell-
known reciprocal influence on cardiac vagal and
sympathetic activity in adults resulting in bra-
dycardia [31, 32]. Despite the above-mentioned
brainstem changes, the striking age-related de-
cline in occurrence of the TCR/DR in adults could
be the result of increased arterial stiffness [32].
In fact, in some instances the HR may rebound
to produce adelayed tachycardia being indicative of
atemporal difference in the activation of the auto-
nomic outflows with the increase in cardiac sympa-
thetic activity outlasting the vagal effect. Indeed, for
the DR, administration of methyl scopolamine may
unmask tachycardia that may then be abolished
by subsequent b-adrenoceptor blockade with pro-
pranolol. In addition, vagally mediated bradycardia
evoked by stimulation of nasopharyngeal receptors
was associated with simultaneous shortening of the
electrocardiogram QT interval, ameasure of ventric-
ular repolarization. Paton et al. suggested that simul-
taneous co-activation may lead to amore efficient
cardiac function, giving greater cardiac output than
activation of the sympathetic limb alone, which is
important when pumping blood into aconstricted
vascular tree as in the case of the DR and TCR [33].
Arterial blood pressure
Despite the increasing clinical reports about the
TCR, the physiological function of this brainstem
reflex is not yet fully explored [3, 33]. The one im-
portant difference is that the typical response of
the DR – or peripheral TCR – is characterized by
arterial hypertension, whereas the “classical” and
central TCR leads to arterial hypotension. Howev-
er, most of the measurements during breath-hold-
ing of blood pressure have shown no or amodest
increase in blood pressure, indicating that the DR
is less effective in humans during breath-hold div-
ing than in mammals.
Cerebral blood flow
Another physiological similarity of both reflex-
es underlines the strong link between both: The
DR results in an increase in cerebral blood flow,
although there is some constriction of the cere-
bral resistance vessels [34]. Astudy revealed that
in untrained BHDs and for apnea of 30s, the CBF
was increased by 60%; in elite BHDs and for the
same apnea time, the CBF could be increased by
200%. The increase in CBF is thus trainable [35].
Trigeminocardiac reflex, diving reflex
and the autonomous nervous system
From aphylogenetic standpoint, the autonomic
nervous system may be considered as astructure
that progressively formed in the course of evolu-
tion in order to increase cardiorespiratory survival.
This hypothesis is further underlined by the fact
that the two main divisions of the autonomic
nervous system – the sympathetic and parasym-
pathetic system – support different types of ex-
change with the external environment. The main
function of the sympathetico-adrenal system is
to organize the function of the visceral organs
for an action to be performed by the organism
in response to the (unexpected) requirements of
the environment (“fight or flight”). On the other
hand, the role of the parasympathetic system is
to prepare the visceral organs for an action to be
performed by the organism on itself: self-protec-
tion (homeostasis), regeneration and recovery and
reproduction. This system strongly underlies phy-
lo- and ontogenetically determined patterns.
The fact that cardiac vagal activity is similar
after stimulation of the TCR and DR supports the
hypothesis that the DR and TCR are closely linked.
Whereas the goal of the DR may be clear (saving
the organism from drowning with an oxygen-con-
serving effect), the purpose of the TCR remains
less obvious.
Trigeminocardiac reflex and diving reflex as
the basis of other pathologies?
The DR is the reflex mechanism most frequent-
ly considered in the etiopathogenesis of sudden
infant death syndrome (SIDS) or crib death [14,
36–38]. This is defined as the sudden, unexpect-
ed death of an infant younger than 1 year of age
which remains unexplained after a thorough in-
vestigation, including acomplete autopsy, exam-
ination of the death scene, and a review of the
clinical history [39].
Recent studies on the pathophysiology of SIDS
have focused on the autonomic nervous system
and have disclosed anomalies – mostly congenital
– located in the brainstem [40–46]. In over 50% of
SIDS cases, histological examination of the brain-
stem on serial sections showed underdevelopment
of the brainstem, e.g. mono-, bilateral or partial hy-
poplasia, delayed neuronal maturation or decreased
neuronal density of the arcuate nucleus, which is an
important center controlling breathing activity. Un-
derdevelopment of the pre-Bötzinger, of the parab-
rachial Kölliker-Fuse complex and of the hypoglossal
nucleus was also detected [38, 41, 42, 44, 46]. Over-
all, the abnormalities of the autonomic nervous sys-
tem described in SIDS may explain the occurrence
of SIDS by vagal inhibition elicited by the DR [40,
43]. In the case of SIDS, apossible role of parenteral
cigarette smoking in the pathogenesis of arcuate
nucleus hypoplasia is discussed, suggesting asimi-
lar defect in patients who are susceptible to the TCR
during neurosurgical operations [43].
Frederic Lemaitre, Tumul Chowdhury, Bernhard Schaller
422 Arch Med Sci 2, April / 2015
Trigeminocardiac reflex, diving reflex
and phylogenesis
As amatter of fact, the oxygen-conserving DR
and its subsets seem to persist in humans [7, 8,
31]. In man, DR may be considered as an archaic
relict which has functional importance in phylo-
genetically lower-ranked animals such as diver
birds or amphibians. The DR is indeed particularly
developed in birds to provide inhibition of cardiac
and breathing activity during underwater feeding,
necessary for individual and species survival [38].
In mammals, the DR is elicited by contact of the
face with cold water and involves breath-holding,
decreased ventilation, bradycardia, intense pe-
ripheral vasoconstriction, and increased MABP,
with the purpose of preventing drowning and
providing an oxygen reservoir in the lungs, main-
taining the heart and the brain adequately oxy-
genated at the expense of less hypoxia-sensitive
organs [47].
In humans, washing the face or plunging into
cold water results in profound bradycardia and re-
distribution of the blood flow to the lungs, brain
and heart [36]. Though considered to be the most
powerful autonomic reflex, the purpose of this re-
flex, especially the breath-hold (BH) response in
humans, is equivocal [47]. In newborns and infants
with adevelopmental defect of the brainstem and
its reflexogenic centers, there were found more
deaths due to apnea or cessation of breathing [14,
36, 38]. Thus the role of the brainstem as part of
the reflex cannot be ignored.
There is fine tuning between the reflex and the
bodily response; however, exaggeration of this
protective response could be detrimental and has
been implicated in causing SIDS. This reflex can
also become manifest in adult with acquired bul-
bospinal disease [38]. In elite BHDs, such problems
after along period of BH training are unknown.
In humans, the DR may be psychologically me-
diated and paradoxically may be lethal. Wolf in
1978 described sudden cardiac death from the
DR in subjects who developed sinus arrest while
thinking of and/or preparing to dive [38, 48].
Thereafter, no similar case has been reported, so
this is arare occurrence. But the DR may be train-
able. It was found that BHDs presented biphasic
HR kinetics and two heart rate decreases [49]. The
second HR decrease, which was concomitant to
the pronounced arterial oxygen saturation (SaO
2
)
decrease, was also simultaneous with amarked
increase in the root mean square successive dif-
ference of the R-R intervals (RMSSD), avagal in-
dex. On the other hand, untrained BHDs showed
only one HR decrease, which appeared before
the concomitant SaO
2
and RMSSD changes. This
study indicates that baroreceptor reflex stimula-
tion and hypoxia may be the key mechanisms in-
volved in producing such abiphasic HR response
of BHDs and thus help in prolongation of BH du-
ration [49].
In fact, the DR had been shown to be effective
in conserving oxygen in humans during BH at
rest [21, 50]. Trained BHDs with severe bradycar-
dia were able to slow the arterial desaturation by
afactor of two or three [50]. This bradycardia is
also accentuated with larger BHD pulmonary vol-
umes before apnea, stimulating the activity in the
slowly adapting pulmonary stretch receptors more
powerfully and resulting in alower HR decrease in
the first phase. The decreasing HR in phase one
also probably accounted for the slight diminution
in cardiac output and, consequently, a slight in-
crease in total peripheral resistance at the end of
this first phase [51]. It would also account for an
increase in stroke volume, which in turn would be
astimulus for the high-pressure aortic and carot-
id baroreceptor [52]. During the second phase, as
BH duration increased and the alveolar volume
decreased, the likely pulmonary volume decreas-
es may have further reduced the activity in the
pulmonary stretch receptors and, consequently,
further reduced the HR [53]. It can be speculated
that hypoxia would result in greater arterial che-
moreceptor stimulation and thus would further
accentuate bradycardia (Figure 1) [15].
Rossi described acase of lethal cardiac arrest
in a young army recruit who succumbed to the
common barracks prank of pouring amesstin of
cold water on the face of asleeping comrade [38].
Abrupt vagal hyperexcitation from an aberrant DR
due to trigeminal-ophthalmic triggering was the
most plausible explanation, but no aimed control
Figure 1. Static apnea of an elite breath-hold diver.
The position is not conventional because usually
they are lying at the surface
The trigeminocardiac reflex – acomparison with the diving reflex in humans
Arch Med Sci 2, April / 2015 423
of the central nervous system was carried out,
suggesting that there may be another reflexogen-
ic arc than in the TCR.
The higher purpose of the TCR in mammals –
especially humans – is at present not fully under-
stood. We think that avery plausible explanation
may be the following: The TCR may be important
for breast-feeding during the first months of life.
At that time the newborn drinks for a relatively
long period of time with its face literally against
the mother. Consequently, the upper airways are
partially obstructed by the mother’s body, result-
ing in hypoventilation. The TCR which is elicited by
mechanical stimulation results in bradycardia, hy-
potension and increase in the cerebral blood flow
in order to avoid damage to the developing brain.
The role of the gastric hypermobility, another typi-
cal reaction elicited by stimulation of the TCR, also
becomes evident from this view. This also may ex-
plain the psychological or emotional dimension of
these reflexes.
Schaller et al. in their studies have also hypoth-
esized on grounds of precise clinical and physio-
logical observations that the term TCR subsumes
the “classical” central TCR and the peripheral DR
or oculocardiac reflex [54]. Grogaard and Sundell
studied the “trigeminal diving reflex” in newborn
lambs, reporting that this reflex is significantly
reduced after treatment with b-adrenergic ago-
nists [55]. As discussed above, we think that even
from aphylogenetic standpoint there is a lot of
evidence that both reflexes are closely linked and
may interact with each other. They are phyloge-
netically old reflexes especially useful for the un-
derwater feeding of diver-birds and amphibians. In
humans they may be important during the breast
feeding period where the babies’ upper airways
are partially obstructed by the close body contact
with the mother. Their role in the pathogenesis of
SIDS and for potential complications during neu-
rosurgical procedures is also highly important. In
fact, abetter understanding of these reflexes will
result in better patient care.
Trigeminocardiac reflex and diving reflex
clinical cases
Trigeminocardiac reflex case
A60-year-old male patient with adiagnosis of
right-sided vestibular schwannoma underwent
tumor resection via a retrosigmoid (suboccipi-
tal approach) approach. His medical history was
significant for long standing hypertension (on
irbesartan – an angiotensin receptor blocker) and
ahistory of smoking (14 PPD). His baseline MABP
was 73 mm Hg and heart rate was 65 beats per
minute. Two hours after skin incision, his MABP
dropped to 43 mm Hg (40.8% drop from base-
line) and concomitantly, his heart rate dropped to
40 beats per minute (38% drop from baseline).
Then, the surgical procedure was discontinued;
he was given atropine 0.6 mg intravenously. Af-
ter 5 min, his MABP and heart rate stabilized to
physiological values and the surgical procedure
was carried out successfully to the end without
any further episodes of TCR. His oxygen saturation
was 100% and no hypercarbia occurred. The post-
operative course was uneventful.
Diving reflex case
An expert BHD (man), 33 years old, with 11
years of BH practice and a forced vital capacity
(FVC) of 6.7 l (124% of predicted values), per-
formed a static BH of 7 min 12 s lying on the
surface in aswimming pool. Heart rate behavior
and SaO
2
were continuously recorded during one
maximal BH. Short-term changes in SaO
2
, HR, the
root mean square successive difference of the R-R
intervals (RMSSD), and the time-domain heart
rate variability (HRV) index were calculated over
the complete BH duration. This BHD presented
biphasic HR kinetics (Figure 2), with two HR de-
creases (32% and 64% of initial HR). The second
HR decrease, which was concomitant to the pro-
nounced SaO
2
decrease, was also simultaneous
with amarked increase in RMSSD. Aclassically un-
trained BHD showed only one HR decrease (about
20–30% of initial HR), which appeared before the
concomitant SaO
2
and RMSSD changes [49].
In fact, for this BHD the cardiovascular diving re-
sponse was effective in conserving oxygen during
BH at rest. This elite BHD with astrong bradycardia
was able to slow the arterial desaturation accord-
ing to previous studies [50]. The BHD also had high-
er FVC than predicted values, which can at the be-
ginning of the BH powerfully stimulate the activity
in the slowly adapting pulmonary stretch receptors
110
100
90
80
70
60
50
40
30
Figure 2. Static BH of 7min and 12s in one expert
BHD. Heart rate [2] and SaO
2
were recorded con-
tinuously before, during and after the BH duration
(presented between the two vertical lines)
0 20 40 60 80 100 120
Time (%)
SaO
2
(%) HR [bpm]
Static BH (7 min 12 s)
Frederic Lemaitre, Tumul Chowdhury, Bernhard Schaller
424 Arch Med Sci 2, April / 2015
and result in astrong HR decrease in the first phase.
The decreasing HR in phase one also probably ac-
counted for the slight diminution in cardiac output
with an increase in stroke volume, which in turn
would be a stimulus for the high-pressure aortic
and carotid baroreceptors [52]. During the second
phase, as BH duration increased, the activity in the
pulmonary stretch receptors would decrease and,
consequently, reduce HR even more [53]. Hypoxia
would also result in greater arterial chemoreceptor
stimulation and would accentuate bradycardia [15].
Thus hypoxia could enhance vasoconstriction and
thus the venous return, stimulating baroreceptors
and again reducing HR [15]. This case indicates that
baroreflex stimulation and hypoxia may be involved
in the biphasic HR response and thus in the long
BH duration and that the DR may be trained.
Current role of trigeminocardiac reflex
vs. diving reflex
Arecent review highlighted the clinical implica-
tions of these reflexes. The DR has been used to
treat supraventricular tachycardia (SVT) [56]. This
reflex is incited by various maneuvers including im-
mersion of the face in preset cold water and breath
holding exercises. Even nasopharyngeal suction
aborted the episodes of SVT in pediatric patients
too [57]. However, arecent animal (pontomedullary
transaction) experiment suggested that the medul-
la and spinal cord may be the primary target site
to complete the reflex arc [58]. On the other hand,
the TCR has been investigated as a protective re-
flex during sleep bruxism [59]. Due to periods of
micro-arousals, tachycardia starts; however, masti-
catory movements rapidly incite the TCR and slow
down the heart rate. Although it was previously
thought that local anesthetic could block incitation
of the TCR, many studies have shown that local an-
esthetic is not effective to blunt the TCR [60, 61].
Similarly, local anesthetic could not blunt the DR ei-
ther. These features indeed highlight the possibility
of differential sensitivity of nerve fibers for inciting
these reflexes, and the stretch could still be reflex-
ogenic even with the blocked nerve. The reflexog-
enic mechanisms of both the reflexes, if not sub-
stantially, may partially share the pathways. The
different receptors and related stimuli may possibly
play acomplex role to elucidate the two different
mechanisms; however, these are still not fully eluci-
dated and warrant further research [62].
Conclusions
There exists aclose association between these
two unique neurogenic reflexes. Both are physio-
logical, protective reflexes and pose some clinical
significance; however, both can be detrimental if
not properly regulated either due to absence of
physiological control or anatomical defect. The DR
can be considered as peripheral asub-form of the
TCR. However, so far, there are no convincing ex-
perimental or histopathological data to prove these
connections, and thus further studies are warrant-
ed. In cases of sudden death attributed to diving or
trigeminal stimulation, meticulous examination of
the brainstem on serial sections may have a cru-
cial role in indentifying morphological substrates
responsible for these reflexes [38, 43, 44, 63–68].
In the future, it will be very interesting to exam-
ine the TCR in elite breath-hold divers who develop
astrong DR.
Conflict of interest
Dr Bernhard Schaller, one of the co-authors of
this review, is the co-editor of the journal (“Ar-
chives of Medical Science”).
The authors declare no conflict of interest.
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