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CARD10 01528
Review
Kothari SS. Mechanism of cyanotic spells in tetralogy of Fallot - the missing link? Int J Cardiol
1992;37:1-5.
The mechanism of cyanotic spells in patients with tetralogy of Fallot is not clear. Increases in
infundibular contractility or hyperpnoea have been considered as the key factors, but this explanation
appears inadequate. In this review, arguments are presented against these commonly held views.
Preliminary evidence is synthesised in favour of another more plausible hypothesis that cyanotic spells
may result from mechanoreceptor stimulation from the right ventricle. Increased contractility (due to
catecholamines) and decreased right ventricular size (due to various factors) can trigger a reflex resulting
in hyperventilation, some peripheral vasodilation without bradycardia, and this may initiate a spell. This
mechanism explains most of the precipitating events and many other issues about cyanotic spells more
satisfactorily.
hyperventilation [93 have been incriminated as was no fall in systolic blood pressure during the
the key factors. spells. The diastolic pressure was not low, nor did
the pulse pressure widen [4,5,7]. Thus, marked
Increase in infundibular contractility vasodilation does not accompany the spells. How-
ever, peripheral vasodilation with amyl nitrite in
Most workers now believe that increase in the patients with tetralogy of Fallot has been
contractility of right ventricular infundibular mus- shown to result in a marked reduction in the
culature results in a decrease in pulmonary blood murmur and increase in cyanosis with relatively
flow, and other features of the cyanotic spells less hypotension [13]. The question of peripheral
[2-4,7,10]. The clinical findings of reduction in vasodilation in cyanotic spells does not seem to
intensity of murmur across the right ventricular have been adequately investigated.
outflow during the spell appear to favour this
view. In fact, marked reduction in forward blood Hyperventilation
flow to the lungs has been angiographically
demonstrated during a spell [lO,ll]. Johnson sug- Hyperpnoea increases oxygen demand and
gested that [12] increase in the contractility may cardiac output [14]. In patients with tetralogy of
result from increase in endogenous nore- Fallot, hyperpnoea results in an increase in arte-
pinephrine (which is possible during most of the rial desaturation due to an increase in right-to-left
precipitating events listed). The salutary effects shunt in the face of increased cardiac output but
of beta-blockers in the patients with spells also a relatively fixed pulmonary blood flow [9]. Gun-
support this view [ll]. theroth et al. suggest that hyperpnoea may be the
The occurrence of spells, albeit rare in pa- important factor initiating and maintaining the
tients with pulmonary atresia and ventricular sep- cyanotic spells [93. To account for the frequent
tal defect, casts doubt on the importance of in- occurrence of spells in the morning hours of the
fundibular contractility as the sole mechanism [7]. day after a good night’s sleep [3], they propose
Furthermore, as discussed below, peripheral va- that the respiratory drive mechanism may be more
sodilation in patients with tetralogy of Fallot may sensitive to changes in blood gases when the
also reduce the intensity of the murmur and patients wake up in a reasonable metabolic status
blood flow to the lungs. Increase in cate- after sleep. During such times a sudden decrease
cholamines has not been demonstrated preceding in arterial p0, and pH and an increase in arterial
the spells. Although an increase in infundibular pC0, induced by a relatively sudden increase in
obstruction may appear a simple explanation of activity, or a Valsalva-like manoeuvre (such as
the spells, it remains to be clarified why every-day crying or bowel movement) may trigger marked
activities like crying, feeding etc. only occasion- hyperpnoea. The hyperpnoea will increase car-
ally result in spells. By itself, an increase in con- diac output and decrease pulmonary blood flow
tractility due to endogenous catecholamines does resulting in further right-to-left shunt and greater
not seem to explain completely the dramatic clin- arterial hypoxaemia. A vicious cycle may thus be
ical presentation of these patients. established resulting in the spell. They also state
that in most of these patients on most days, there
Peripheral vasodilation is either an adjustment in sensitivity of respira-
tory drive mechanism or an adjustment in bicar-
Peripheral vasodilation in patients with tetral- bonate, which prevents the occurrence of spells
ogy of Fallot would increase shunting of the right [93. This elusive sequence of events has never
ventricular blood to the aorta through ventricular been proved or disproved. Furthermore, it does
septal defect, and decrease pulmonary blood flow. not explain the fact that spells indeed occur at
Previously suggested by Hamilton [8] as an impor- any time of the day [4]. Moreover, it may be
tant reason for the cyanotic spells, subsequent relevant to note that the sensitivity of the respira-
workers did not consider it important as there tory centre to hypoxia is known to be blunted in
patients with cyanotic heart disease [15], and is ture on saturation in patients with tetralogy of
not restored even years after corrective surgery Fallot, Lurie reported precipitating hyperventila-
1161. tion and syncope (spell) in a patient during a tilt
In the absence of any better alternative the to 70” [22]. It is recognised that the right ventricle
scheme suggested by Guntheroth et al. has pro- is only sparsely innervated [181, and more recent
vided a good working hypothesis up to now. How- experimental studies indicate no important role
ever, I believe that the following hypothesis may of right ventricle mechanoreceptors in Gardiac or
explain the mechanism of spells and the events respiratory control normally [231. However, the
precipitating these spells more satisfactorily. situation in tetralogy of Fallot wherein the
anatomy is altered, may be different from nor-
Hypothesis mals. The hypertrophied ventricular walls, ro-
tated conal septum, or other factors may be im-
The cyanotic spells in patients with tetralogy of portant. How the increase in catecholamines and
Fallot may result from the stimulation of right decrease in the cavity size in this distinct
ventricular mechanoreceptors. Increased contrac- pathoanatomy of tetralogy of Fallot predispose
tility (due to endogenous catecholamines), and a the receptors to trigger responses remains to be
decrease in right ventricular cavity size (such as established. It may be relevant that amongst the
can occur with Valsalva-like manoeuvre) may patients with tetralogy of Fallot, a slightly differ-
trigger a reflex response resulting in hyperventila- ent anatomy is seen from that in patients who
tion, some peripheral vasodilation, without brady- present with frequent cyanotic spells [24].
cardia. The hyperpnoea may perpetuate a vicious The relationship of precipitating events seems
cycle, as discussed previously. It is well known clearer with the proposed mechanisms.
now that a combination of decreased left ventric- (a> Crying, defaecation, suprauentricular tachy-
ular volume and raised sympathetic tone may cardia and feeding: It is easy to envisage in-
stimulate left ventricular mechanoreceptors that creased contractility due to catecholamines and
may trigger marked peripheral vasodilation and decreased cavity size of the right ventricle during
bradycardia (vasovagal syncope) [17]. The ventric- crying, bowel movement (due to Valsalva-like ma-
ular receptors are a heterogeneous population of noeuvre) or supraventricular tachycardia (due to
receptor subgroups with varying thresholds of ac- shortened diastole) [25] that can induce a cyan-
tivation, and varying reflex effects [18]. Response otic spell. Similarly feeding also induces increase
to some vagal afferents may not alter heart rate in cardiac output and heart rate and decrease in
1181,but may cause hyperventilation and periph- cavity size [26].
eral vasodilation. The response to left ventricular (b) Hot weather, infections: Peripheral vasodi-
and right ventricular receptor stimulation may lation during summer, or with infection [27] facili-
also differ [ 191. Experimental mechanoreceptor tates better emptying of right ventricle into aorta.
stimulation from the right ventricle in sympathec- This could reduce the cavity size and may in-
tomised dogs has been reported to cause hyper- crease the susceptibility to cyanotic spells.
ventilation and hypotension without bradycardia Cc) Cardiac catheterization : Direct mechanical
[20]. Moreover, in some of the head-up tilt table stimulation of the receptors by a cardiac catheter
studies done to provoke left ventricular mechano- 151may induce a cyanotic spell. Dehydration due
receptors and vasovagal response, a few patients to overnight fasting (which may decrease the right
develop marked hyperventilation without brady- ventricular size), or peripheral vasodilation in-
cardia or hypotension 117,211. Although the au- duced by premeditation may also be contributory.
thors did not comment on this, it may be specu- Cd) Time of the day: The more frequent occur-
lated that receptors from the right ventricle rence of spells during the morning hours may
elicited such a response. Such studies in patients relate to catecholamine secretion on awakening
with tetralogy of Fallot would be interesting. In- or to circadian variations in the endogenous cate-
deed, in 1953 while studying the effects of pos- cholamines secretions [2X].
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