Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans

Abstract

High altitude-induced hypoxia in humans evokes a pattern of breathing known as periodic breathing (PB), in which the regular oscillations corresponding to rhythmic expiration and inspiration are modulated by slow periodic oscillations. r The phase coherence between instantaneous heart rate and respiration is shown to increase significantly at the frequency of periodic breathing during acute and sustained normobaric and hypobaric hypoxia. r It is also shown that polymorphism in specific genes, NOTCH4 and CAT, is significantly correlated with this coherence, and thus with the incidence of PB. r Differences in phase shifts between blood flow signals and respiratory and PB oscillations clearly demonstrate contrasting origins of the mechanisms underlying normal respiration and PB. r These novel findings provide a better understanding of both the genetic and the physiological mechanisms responsible for respiratory control during hypoxia at altitude, by linking genetic factors with cardiovascular dynamics, as evaluated by phase coherence.

Variability in hypoxic response: Could genetics play a role?

“…For example, EGLN1 and EPAS1 play an important role in determining the variability in response to hypobaric hypoxia at altitude (Simonson et al 2010) and have been linked to the development of polycythemia and associated abnormalities. However, we are unclear as to how Lancaster et al (2020) determined their candidate genes of interest given that the general categories mentioned encompass many potentially relevant genes, and we encourage further development in this area in such studies.…”

“…Similarly, patients with congestive heart failure can develop Cheyne Stokes breathing (CSB), which has been somewhat controversial as a result of uncertainty about its prognostic impact and its optimal therapy (Bradley et al 2005). In this issue of The Journal of Physiology, the new findings reported by Lancaster et al (2020) not only shed new light on these issues, but also raise broader questions about genetic susceptibility to various breathing patterns and their associated consequences.…”

“…Given the variable prognosis of CSB and the inconsistent results of therapeutic studies to eliminate CSB, there is probably individual variability in the occurrence of CSB and in its haemodynamic and neurocognitive consequences (Heinrich et al 2019). Lancaster et al (2020) report possible associations with oxidative stress genes, which, in theory, could determine which patient may be susceptible to CSB. In particular, the selected anti-oxidative genes play a role in defence against oxidative stress, and the NOTCH signalling pathway interacts with hypoxia sensing pathways and plays an important role in neurodevelopment.…”

“…Third, would sophisticated autonomic physiology assessments (e.g. muscle sympathetic nerve activity) help to elucidate the mechanism underlying the cardiorespiratory phase coherence found by Lancaster et al (2020).…”

“…In this issue of The Journal of Physiology , the new findings reported by Lancaster et al . (2020) not only shed new light on these issues, but also raise broader questions about genetic susceptibility to various breathing patterns and their associated consequences.…”