Chemoreflex Sensitivity In Patients Research Articles

Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex, and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53 ± 10 yr, 29.2 ± 5.8 kg/m2, apnea-hypopnea index = 17.8 ± 8.1, 43%F) completed three visits. Resting brachial blood pressure and cardiopulmonary responses to inspiratory hypoxia were measured before, and 2 h after, acute inorganic nitrate supplementation [∼0.10 mmol (placebo), 4.03 mmol (low dose), and 8.06 mmol (high dose)]. Placebo increased neither plasma [nitrate] (30 ± 52 to 52 ± 23 μM, P = 0.26) nor [nitrite] (266 ± 153 to 277 ± 164 nM, P = 0.21); however, both increased following low (29 ± 17 to 175 ± 42 μM, 220 ± 137 to 514 ± 352 nM) and high doses (26 ± 11 to 292 ± 90 μM, 248 ± 155 to 738 ± 427 nM, respectively, P < 0.01 for all). Following placebo, systolic blood pressure increased (120 ± 9 to 128 ± 10 mmHg, P < 0.05), whereas no changes were observed following low (121 ± 11 to 123 ± 8 mmHg, P = 0.19) or high doses (124 ± 13 to 124 ± 9 mmHg, P = 0.96). The peak ventilatory response to hypoxia increased following placebo (3.1 ± 1.2 to 4.4 ± 2.6 L/min, P < 0.01) but not low (4.4 ± 2.4 to 5.4 ± 3.4 L/min, P = 0.11) or high doses (4.3 ± 2.3 to 4.8 ± 2.7 L/min, P = 0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P = 0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.NEW & NOTEWORTHY The present study is the first to examine the acute effects of inorganic nitrate supplementation on resting blood pressure and cardiopulmonary responses to hypoxia (e.g., peripheral chemoreflex sensitivity) in patients with obstructive sleep apnea (OSA). Our data indicate inorganic nitrate supplementation attenuates an early-morning rise in systolic blood pressure potentially attributable to blunted peripheral chemoreflex sensitivity. These data show proof-of-concept that inorganic nitrate supplementation could reduce the risk of cardiovascular disease in patients with OSA.

Peripheral chemoreflex sensitivity in patients with heart failure and preserved inspiratory muscle strength

Individuals with chronic heart failure (CHF) and inspiratory muscle weakness exhibit na exacerbated peripheral chemoreflex sensitivity (PCS) in relation to patients with preserved inspiratory muscle strength. However, it remains unclear wether patients with CHF patients with preserved inspiratory muscle strength show PCS similar to healthy individuals. The objective of this study was to compare PCS between patients with CHF and preserved inspiratory muscle strength and healthy individuals. Ten subjects with CHF (55 ± 8 years old) and 10 healthy subjects (54 ± 7 years old) matched for sex and age participated in this study. All subjects showed preserved inspiratory muscle strength, which was measured through a pressure transducer. PCS was obtained through the technique of transient hypoxia induced by the inhalation of pure nitrogen, which was repeated for 10 times. PCS was calculated by linear regression analysis between maximal ventilation and lower oxygen saturation. PCS in patients with CHF and preserved inspiratory muscle strength (1.09 ± 0.95 L.min −1 .% SaO 2 −1 ) did not differ from healthy subjects (0.70 ± 0.73 L.min −1 .% SpO 2 −1 ; P = 0.31). There was a significant association between PCS and inspiratory muscle strength ( r = 0.58, P = 0.006), however only 19% of variance in PCS may be explained by inspiratory muscle strength. Patients with CHF and preserved inspiratory muscle strength show PCS similar to healthy individuals.

Evaluation of Breath-Holding Test in Assessment of Peripheral Chemoreflex Sensitivity in Patients with Chronic Heart Failure.

Background:The sensitivity of peripheral chemoreflex is a marker of the severity of heart failure and the prognosis of the outcome in these patients. The assessment of chemosensitivity in these patients remains an actual problem.Objective:The aim of the study was to explore the relationship between a Breath-Holding Test (BHT) and single-breath carbon dioxide test and to evaluate the reliability of both tests in patients with Heart Failure (HF).Method:The study was performed in 43 patients with chronic heart failure. All subjects underwent BHT and single-breath carbon dioxide (CB-CO2), the evaluation of both tests was repeated a month later. Relationship of two test was evaluated by correlation analysis. Reliability was assessed with calculation of Standard Error of Measurement (SEM), Coefficient of Variation (CV) and Intraclass Correlation Coefficient (ICC).Results:The duration of the breath-holding was inversely correlated to the result of CB-CO2 test (r = -0.86 at first measurement and r = -0.79 after a month) The ICC was 0.87 (95%CI: 0.78–0.93) for SB-CO2 test and 0,93 (95%CI: 0.88–0.96) for BHT, the CV was 24% for SB-CO2 and 13% for BHT. SEM for SB-CO2 test was 0.04 L / min / mmHg and limits of variation was 0.11 L / min / mmHg; SEM for BHT was 3.6 sec and limits of variation was10 sec.Conclusion:Breath-holding test is a reliable and safe method for assessing the sensitivity of peripheral chemoreflex to carbon dioxide in patients with heart failure.

Obstructive sleep apnea is associated with increased chemoreflex sensitivity in patients with metabolic syndrome.

Obstructive sleep apnea (OSA) is often observed in patients with metabolic syndrome (MetS). In addition, the association of MetS and OSA substantially increases sympathetic nerve activity. However, the mechanisms involved in sympathetic hyperactivation in patients with MetS + OSA remain to be clarified. We tested the hypothesis that chemoreflex sensitivity is heightened in patients with MetS and OSA. Prospective clinical study. Forty-six patients in whom MetS was newly diagnosed (ATP-III) were allocated into: (1) MetS + OSA (n = 24, 48 ± 1.8 yr); and (2) MetS - OSA (n = 22, 44 ± 1.7 yr). Eleven normal control subjects were also studied (C, 47 ± 2.3 yr). OSA was defined as an apnea-hypopnea index ≥ 15 events/hr (polysomnography). Muscle sympathetic nerve activity (MSNA) was measured by microneurography technique. Peripheral chemoreflex sensitivity was assessed by inhalation of 10% oxygen and 90% nitrogen (carbon dioxide titrated), and central chemoreflex sensitivity by 7% carbon dioxide and 93% oxygen. Physical characteristics and MetS measures were similar between MetS + OSA and MetS - OSA. MSNA was higher in MetS + OSA patients compared with MetS - OSA and C (33 ± 1.3 versus 28 ± 1.2 and 18 ± 2.2 bursts/min, P < 0.05). Isocapnic hypoxia caused a greater increase in MSNA in MetS + OSA than MetS - OSA and C (P = 0.03). MSNA in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.005). Further analysis showed a significant association between baseline MSNA and peripheral (P < 0.01) and central (P < 0.01) chemoreflex sensitivity. Min ventilation in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.001). OSA increases sympathetic peripheral and central chemoreflex response in patients with MetS, which seems to explain, at least in part, the increase in sympathetic nerve activity in these patients. In addition, OSA increases ventilatory central chemoreflex response in patients with MetS.

Abstract 12935: Hypocaloric Diet and Exercise Training Improves the Chemoreflex Sensitivity in Patients with Metabolic Syndrome and Obstructive Sleep Apnea

Cristiane Maki-Nunes, 2011 Finalist and Presenting Author

Effect of Treatment With Nasal Continuous Positive Airway Pressure on Ventilatory Response to Hypoxia and Hypercapnia in Patients With Sleep Apnea Syndrome

The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. Sleep laboratory of Azienda Ospedaliera Garibaldi. Twenty-five patients with moderate-to-severe OSA. Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.

Dobutamine potentiates the peripheral chemoreflex in patients with congestive heart failure

Backgroundβ-Adrenergic agonists may increase chemoreflex sensitivity to hypoxia in normal humans. Chemoreflex function is important in the pathophysiology of heart failure. Whether the β-1 agonist dobutamine, which is frequently administered to patients with heart failure, alters their chemoreflex sensitivity is not known. MethodsWe tested the hypothesis that dobutamine increases chemoreflex sensitivity in patients with congestive heart failure (CHF) using a randomized, double-blinded, placebo-controlled study design. We assessed the influence of dobutamine on minute ventilation and hemodynamics during normoxic breathing and during peripheral chemoreflex deactivation by hyperoxia (100% O2) in 9 patients with CHF. ResultsDobutamine increased minute ventilation in patients with CHF (9.4±0.9 versus 8.4±0.7 L/min, P=.005) during normoxia. Peripheral chemoreflex deactivation by hyperoxia suppressed the ventilatory effects of dobutamine (10.4±1.4 L/min for dobutamine versus 10.0±1.2 L/min for placebo, P=.34). ConclusionsDobutamine increases ventilation during normoxia, but not during hyperoxia in patients with CHF. We conclude that dobutamine enhances peripheral chemoreflex sensitivity in patients with congestive heart failure.

Assessment of chemoreflex sensitivity in free breathing young subjects by correction for respiratory influence

Background: The assessment of autonomic function is an important tool for risk stratification in critically ill patients. Peripheral cardiac chemoreflex sensitivity has been considered a marker for increased risk of sudden cardiac death. In normals, the evaluation of peripheral cardiac chemoreflex sensitivity is performed under controlled breathing conditions during inhalation of hypoxic gas. Since this is poorly tolerated by patients, they are commonly studied under hyperoxic conditions, which are not physiological. Methods: We studied 20 healthy volunteers who underwent free and controlled breathing of a hypoxic gas mixture (10% O 2 in N 2) over 5 min. Values of peripheral cardiac chemoreflex sensitivity, corrected for respiratory influence, were compared with the results obtained experimentally under controlled breathing conditions in the same subjects. Results: We found a substantial difference between values obtained during free and controlled breathing (3.64±0.81 vs. 1.53±0.32 ms/mmHg, respectively; P<0.05). After application of a respiratory correction, described and validated in this article, no significant difference was seen for these values (0.89±0.91 vs. 1.53±0.32 ms/mmHg, P=0.46). Conclusions: This approach allows the evaluation of peripheral cardiac chemoreflex sensitivity in free breathing subjects. This correction could improve the assessment of cardiac chemoreflex sensitivity in patients with cardiorespiratory disorders, who find it difficult to control their breathing according to an experimental protocol.