Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia

Sangkatumvong, Suvimol; Coates, Thomas D.; Khoo, Michael C. K.

doi:10.1088/0967-3334/29/5/010

Cited by 32 publications

(32 citation statements)

References 41 publications

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“…This confirms the results of previous studies that, in the absence of any concomitant disease, anemia is associated with sympathetic activation. 15,16 However, these observations refer to anemia not associated with CHF, and this link has been extrapolated to CHF-related anemia without any pathophysiological evidence, until our study. 12 Our findings, on the basis of direct recording of sympathetic nervous system (SNS) activity in patients with CHF-related anemia, are the first evidence that such a link exists.…”

Section: Discussionmentioning

confidence: 93%

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

et al. 2010

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Abstract-Sympathetic activation contributes to both the initiation and progression of heart failure. The role of anemia in determining sympathetic overactivity in chronic heart failure (CHF) patients is unknown. We tested the hypothesis that, in CHF patients, anemia could lead to increased sympathetic activity through tonic activation of excitatory chemoreceptor afferents. We conducted a double-blind, randomized, vehicle-controlled study to examine the effect of chemoreflex deactivation on muscle sympathetic nerve activity in CHF patients with and without anemia. We compared the effect of breathing 100% oxygen for 15 minutes in 18 stable CHF patients with anemia and 18 control CHF patients matched for age, sex, blood pressure, and body mass index. Baseline muscle sympathetic nerve activity was significantly elevated in CHF patients with anemia compared with patients with CHF alone (56.0Ϯ3.2 versus 45.5Ϯ3.1 bursts per minute; PϽ0.0237). Administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity in CHF patients with anemia (from 56.0Ϯ3.4 to 50.9Ϯ3.2 bursts per minute; PϽ0.0019). In contrast, neither room air nor 100% oxygen changed muscle sympathetic nerve activity or hemodynamics in patients with CHF alone. We report for the first time direct evidence of increased sympathetic nerve traffic in patients with CHF-related anemia. Sympathetic hyperactivity in patients with CHF and anemia is partially chemoreflex mediated and could explain how anemia contributes to the progression of CHF and increases morbidity and mortality in these patients. (Hypertension. 2010;55:1012-1017.)

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Section: Discussionmentioning

confidence: 93%

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

et al. 2010

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“…Moreover, because respiration causes sinusoidal variations in heart rate (17), we compensated for the effects of changes in breathing patterns on HRV by using the respiratory waveform (18). Consequently, the respiratory-adjusted ANS data presented here represent all autonomic inputs other than respiration.…”

Section: Assessment Of the Ans Responsesmentioning

confidence: 99%

“…We denoted respiratory-adjusted HFP and LHR as HFP ra and LHR ra . We have published the details of these computations elsewhere (18)(19)(20). For additional information of the experimental method and data analysis technique, see the online supplement.…”

Section: Assessment Of the Ans Responsesmentioning

confidence: 99%

“…Because changes in heart rate and perfusion are controlled by the sympathetic and parasympathetic nervous system, we measured the sympathetic-parasympathetic balance using frequency domain analysis of HRV. By using a novel methodology that permits quantitation of ANS components over short time periods, we were able to study ANS changes in response to hypoxia while removing contributions to HRV caused by normal respiration (18,26,27). An example of the change in RRI (panel D) with respect to hypoxia (panel A) is seen in Figure 2.…”

Section: Physiologic Responses To Transient Hypoxiamentioning

confidence: 99%

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Peripheral Vasoconstriction and Abnormal Parasympathetic Response to Sighs and Transient Hypoxia in Sickle Cell Disease

Sangkatumvong¹,

Khoo²,

Kato

et al. 2011

Am J Respir Crit Care Med

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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 sighinduced 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.Keywords: hypoxia; autonomic nervous system; respiration; vasoconstriction; sickle cell disease Sickle cell disease (SCD) is an inherited blood disorder that results from an amino acid substitution in the b globin chain of hemoglobin, producing sickle hemoglobin (HbS) (1, 2). HbS polymerizes when it releases oxygen to tissues, causing the normally flexible red blood cells to become rigid and to obstruct blood flow (3). The subsequent ischemia results in chronic organ damage and ultimately premature death (3-5). Although SCD is caused by a single amino acid substitution, significant variability in the frequency of overt sickling episodes has been reported among subjects with the same genotype, suggesting that other factors cause the transition from steady-state sickling to full vasoocclusive crisis (VOC).The specific factors that affect this transition are incompletely understood. Flexible, oxygenated, HbS-containing red blood cells (SRBC) traverse capillaries and release their oxygen. After HbS releases its oxygen, it polymerizes after a short delay and the SRBC become rigid (6). If the SRBC fail to escape the microvasculature within the delay time period, the SRBC become lodged. Thus, any factor that increases the SRBC transit time or shortens t...

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“…However, although it has been suggested that ANS activity could be involved in the pathophysiology of SCA, the mechanisms by which ANS imbalance might modulate the clinical severity of SCA are still poorly understood. 12,13 In an effort to gain further insight into the relationship between ANS activity and clinical expression of SCA, we compared the ANS activity pattern of SCA patients with frequent severe pain crises within the previous year with that of SCA patients who had not experienced any pain crises during this same time, and with a control group made up of healthy subjects. In addition, since associations between blood rheology, inflammation and ANS activity have been proposed in other diseases, 14,15 hematologic, blood viscosity and inflammatory markers were compared between the three groups.…”

Section: Introductionmentioning

confidence: 99%

Frequency of pain crises in sickle cell anemia and its relationship with the sympatho-vagal balance, blood viscosity and inflammation

Bowers²,

et al. 2011

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BackgroundRecent evidence suggests that autonomic nervous system activity could be involved in the pathophysiology of sickle cell disease, but it is unclear whether differences in autonomic nervous system activity are detectable during steady state in patients with mild and severe disease. The aim of the present study was to compare the autonomic nervous system activity, blood rheology, and inflammation in patients with sickle cell anemia according to the frequency of acute pain crisis. Design and MethodsTwenty-four healthy volunteers, 20 patients with sickle cell anemia with milder disease, and 15 patients with sickle cell anemia with more severe disease were recruited. Milder disease was defined as having no pain crisis within the previous year. More severe disease was defined as having had within the previous year three or more pain crises which were documented by a physician and required treatment with narcotics. The autonomic nervous system activity was determined by spectral analysis of nocturnal heart rate variability. Blood viscosity determination and measurements of several inflammatory markers (interleukin-6, soluble vascular cell adhesion molecule-1, soluble CD40 ligand and sL-selectin) were made on blood samples collected in steady-state conditions. ResultsResults showed that: 1) patients who had suffered more frequent pain crises had lower parasympathetic activity and greater sympatho-vagal imbalance than both controls and patients with milder disease. However, when adjusted for age, no significant difference was detected between the two sickle cell anemia patient groups; 2) patients who had suffered more frequent pain crises had higher blood viscosity than patients with milder disease, and this was not dependent on age. ConclusionsResults from the present study indicate that both the autonomic nervous system activity and blood viscosity are impaired in patients with sickle cell anemia exhibiting high frequency of pain crisis in comparison with those who did not experience a crisis within the previous year. Haematologica 2011;96(11):1589-1594. doi:10.3324/haematol.2011 This is an open-access paper. Frequency of pain crises in sickle cell anemia and its relationship with the sympatho-vagal balance, blood viscosity and inflammation

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Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia

Cited by 32 publications

References 41 publications

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

Peripheral Vasoconstriction and Abnormal Parasympathetic Response to Sighs and Transient Hypoxia in Sickle Cell Disease

Frequency of pain crises in sickle cell anemia and its relationship with the sympatho-vagal balance, blood viscosity and inflammation

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