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Brain & Heart Sleep and limb vasodilation

and in the forearm (32.6%, P < 0.0001). Simultaneously, 3.2. Circadian rhythm in hypertensive patients
arterial resistance mirrored the trend of flow (−33.5%, As previously mentioned, our initial experiments were
P < 0.001 in the leg; −32.7%, P < 0.001 in the forearm). 46-50 conducted on young, healthy, normotensive volunteers.
Given the expected nocturnal decrease in BP and heart Subsequently, the same circadian rhythm was identified in
rate, and considering that subjects maintained a constant 35 untreated hypertensive patients with an average systolic
clinostatic posture while adhering to a standardized 24-h BP of 142.2 ± 16.2/89.7 ± 9.1 mmHg. In these hypertensive
protocol, it became evident that elevated limb arterial flow subjects, forearm blood flow exhibited an increase (32.2%,
could only be attributed to a sleep-induced arterial flow P < 0.0001), while forearm resistance exhibited a decrease
redistribution resulting from limb vasodilation. Figure 1
illustrates the 24-h leg flow of the very first subject as a (-33%, P < 0.0001) during sleep compared to waking
48,50
representative example, with similar patterns observed in hours. These observations were consistent across
50
subsequent cases. 46-50 Crucially, in all cases, the variation different age groups, mirroring the trend previously
in leg and forearm flow started earlier than the anticipated observed in normotensive individuals.
sleep-induced BP decline. This finding confirms that sleep- 3.3. Circadian rhythm in heart transplant recipients
induced hemodynamic variations were the plausible cause,
not the consequence, of the observed differences in the We sought to investigate whether the circadian rhythm in
24-h BP pattern. 8,47,48 limb arterial flow and resistance during sleep and waking
hours is influenced by cardiac activity, which notably
These fundamental pilot experiments, performed differs between the two states. To address this, we focused
with the methodologies grounded in human physiology, on heart transplant recipients, a group previously shown to
indicated for the first time that the hemodynamic pattern in lack a day/night (rather than wake/sleep) BP rhythm. 51,52
the limbs differed significantly during waking hours (lower Our goal was to determine whether the circadian rhythm
flow and higher resistance) compared to sleep (higher flow in limb arterial flow and resistance during sleep persists in
and lower resistance). The confinement of subjects to bed heart transplant recipients, shedding light on whether the
in these experiments convinced us that this circadian alternation between limb vasodilation and vasoconstriction
rhythm in limb arterial flow and resistance was intrinsic during sleep is influenced by cardiac activity and its
and independent of daily activity. This finding not only impact on arteriolar tone. The orthotopic heart transplant,
fueled our commitment to the research program but also performed according to the Shumway technique with
motivated our exploration into the underlying causes of atrial cuffs suture and termino-terminal anastomosis of the
what appeared to be a redistribution of blood to the limbs
during sleep. Drawing inspiration from prior research ascending aorta and pulmonary truncus before bifurcation,
demonstrating varying arterial flow and adrenergic drive notoriously leads to the loss of vagally mediated as well as
53,54
in different organs throughout the day (although not sympathetic-mediated heart control. Consequently, the
specifically in relation to sleep), such as the kidney and transplanted heart has no role in the autonomic control of
liver, 10,11 we postulated that the variations in limb circulation peripheral hemodynamics. A previous spectral analysis
represented a counter-regulatory mechanism – a form of performed the day before the 24-h bed study confirmed
blood reservoir essential for maintaining the characteristic that heart-transplant recipients differed significantly from
“lower BP” associated with sleep. controls in this respect, exhibiting the expected lower
heart rate variability for both low and high frequencies
(Figure 2). 49

In these subjects, leg arterial flow was found to be
higher (26.6%, P < 0.0001), and leg resistance lower
(-36.6%, P < 0.0001) during sleep compared to waking
hours, mirroring the patterns observed in controls with
native hearts. This outcome confirms that heart nerves do
not contribute to sleep-dependent control of limb flow and
resistance variations. 49
3.4. Circadian rhythm in patients with spinal cord
Figure 1. Plethysmographic monitoring of leg arterial flow
(in mL × min ) in our very first case, a normotensive health volunteer transection
-1
man age 26 years confined to bed for 24 h constantly by an orthopedic The question of how sleep-induced variations in limb arterial
device. The other cases of our pilot studies in normal subjects had the
46
same trend. The red line indicates the sleeping hours directly verified by flow and resistance occur remained to be clarified. Previous
a professional observer. studies demonstrated that the day/night rhythm (distinct

Volume 2 Issue 1 (2024) 3 https://doi.org/10.36922/bh.1886