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Am J Respir Crit Care Med. 2011 Aug 15;184(4):474-81. doi: 10.1164/rccm.201103-0537OC.

Peripheral vasoconstriction and abnormal parasympathetic response to sighs and transient hypoxia in sickle cell disease.

Author information

1
Biomedical Engineering Department, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Abstract

RATIONALE:

Sickle cell disease is an inherited blood disorder characterized by vasoocclusive crises. Although hypoxia and pulmonary disease are known risk factors for these crises, the mechanisms that initiate vasoocclusive events are not well known.

OBJECTIVES:

To study the relationship between transient hypoxia, respiration, and microvascular blood flow in patients with sickle cell.

METHODS:

We established a protocol that mimics nighttime hypoxic episodes and measured microvascular blood flow to determine if transient hypoxia causes a decrease in microvascular blood flow. Significant desaturations were induced safely by five breaths of 100% nitrogen.

MEASUREMENTS AND MAIN RESULTS:

Desaturation did not induce change in microvascular perfusion; however, it induced substantial transient parasympathetic activity withdrawal in patients with sickle cell disease, but not controls subjects. Marked periodic drops in peripheral microvascular perfusion, unrelated to hypoxia, were triggered by sighs in 11 of 11 patients with sickle cell and 8 of 11 control subjects. Although the sigh frequency was the same in both groups, the probability of a sigh inducing a perfusion drop was 78% in patients with sickle cell and 17% in control subjects (P < 0.001). Evidence for sigh-induced sympathetic nervous system dominance was seen in patients with sickle cell (P < 0.05), but was not significant in control subjects.

CONCLUSIONS:

These data demonstrate significant disruption of autonomic nervous system balance, with marked parasympathetic withdrawal in response to transient hypoxia. They draw attention to an enhanced autonomic nervous system–mediated sigh–vasoconstrictor response in patients with sickle cell that could increase red cell retention in the microvasculature, promoting vasoocclusion.

Comment in

PMID:
21616995
PMCID:
PMC3175540
DOI:
10.1164/rccm.201103-0537OC
[Indexed for MEDLINE]
Free PMC Article

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