scholarly journals Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure

2020 ◽  
Vol 11 ◽  
Author(s):  
Daniel A. Keir ◽  
James Duffin ◽  
John S. Floras
Keyword(s):  
Heart Failure ◽  
Carotid Body ◽  
Vascular Function ◽  
Ventilatory Response ◽  
Arterial Oxygen Tension ◽  
Arterial Oxygen ◽  
Patient Specific ◽  
Hypoxic Exposure ◽  
Chemoreflex Sensitivity ◽  
Peripheral Chemoreflex

Heart failure with reduced ejection fraction (HFrEF) induces chronic sympathetic activation. This disturbance is a consequence of both compensatory reflex disinhibition in response to lower cardiac output and patient-specific activation of one or more excitatory stimuli. The result is the net adrenergic output that exceeds homeostatic need, which compromises cardiac, renal, and vascular function and foreshortens lifespan. One such sympatho-excitatory mechanism, evident in ~40–45% of those with HFrEF, is the augmentation of carotid (peripheral) chemoreflex ventilatory and sympathetic responsiveness to reductions in arterial oxygen tension and acidosis. Recognition of the contribution of increased chemoreflex gain to the pathophysiology of HFrEF and to patients’ prognosis has focused attention on targeting the carotid body to attenuate sympathetic drive, alleviate heart failure symptoms, and prolong life. The current challenge is to identify those patients most likely to benefit from such interventions. Two assumptions underlying contemporary test protocols are that the ventilatory response to acute hypoxic exposure quantifies accurately peripheral chemoreflex sensitivity and that the unmeasured sympathetic response mirrors the determined ventilatory response. This Perspective questions both assumptions, illustrates the limitations of conventional transient hypoxic tests for assessing peripheral chemoreflex sensitivity and demonstrates how a modified rebreathing test capable of comprehensively quantifying both the ventilatory and sympathoneural efferent responses to peripheral chemoreflex perturbation, including their sensitivities and recruitment thresholds, can better identify individuals most likely to benefit from carotid body intervention.

Acute hypoxic ventilation, carotid body cell division, and dopamine content during early hypoxia in rats

1995 ◽  
Vol 79 (5) ◽  
pp. 1504-1511 ◽  
Author(s):  
D. Bee ◽  
D. J. Pallot
Keyword(s):  
Carotid Body ◽  
Cellular Proliferation ◽  
Dopamine D2 Receptor ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Control Level ◽  
Arterial Oxygen ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
Dopamine Content

In a previous study, we showed that the acute hypoxic ventilatory response was blunted in anesthetized chronically hypoxic rats and was restored by blockade of the dopamine D2 receptor with domperidone. We now report observations made during 1–8 days of exposure to 10% O2 on the acute hypoxic ventilatory response and the effect of domperidone and relate them to dopamine content and cellular proliferation in the carotid body. Hypoxic exposure caused a parallel shift in the hypoxic response curve to higher levels of ventilation and arterial oxygen saturation. The greatest response occurred on day 1 and was unaffected by domperidone: dopamine content diminished and mitotic activity increased. By 8 days, hypoxic ventilation approached normal and was significantly augmented by domperidone; in the carotid body, dopamine levels had risen above the control level and mitoses had diminished. Thus the increase in ventilation was inversely related to carotid body dopamine content, which was depressed. The possibility of a causal relationship is discussed.

scholarly journals Downregulation of carbon monoxide as well as nitric oxide contributes to peripheral chemoreflex hypersensitivity in heart failure rabbits

2008 ◽  
Vol 105 (1) ◽  
pp. 14-23 ◽  
Author(s):  
Yanfeng Ding ◽  
Yu-Long Li ◽  
Harold D. Schultz
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Carbon Monoxide ◽  
Sympathetic Nerve ◽  
No Donor ◽  
Renal Sympathetic Nerve ◽  
Chemoreflex Sensitivity ◽  
Tubulin Protein ◽  
Peripheral Chemoreflex ◽  
Renal Sympathetic

Peripheral chemoreflex sensitivity is potentiated in clinical and experimental chronic heart failure (CHF). Downregulation of nitric oxide (NO) synthase (NOS) in the carotid body (CB) is involved in this effect. However, it remains poorly understood whether carbon monoxide (CO) also contributes to the altered peripheral chemoreflex sensitivity in CHF. This work highlights the effect of NO and CO on renal sympathetic nerve activity (RSNA) in response to graded hypoxia in conscious rabbits. Renal sympathetic nerve responses to graded hypoxia were enhanced in CHF rabbits compared with sham rabbits. The NO donor S-nitroso- N-acetylpenicillamine (SNAP, 1.2 μg·kg−1·min−1) and the CO-releasing molecule tricarbonyldichlororuthenium (II) dimer {[Ru(CO)3Cl2]2, 3.0 μg·kg−1·min−1} each attenuated hypoxia-induced RSNA increases in CHF rabbits ( P < 0.05), but the degree of attenuation of RSNA induced by SNAP or [Ru(CO)3Cl2]2 was smaller than that induced by SNAP + [Ru(CO)3Cl2]2. Conversely, treatment with the NOS inhibitor Nω-nitro-l-arginine (30 mg/kg) + the heme oxygenase (HO) inhibitor Cr (III) mesoporphyrin IX chloride (0.5 mg/kg) augmented the renal sympathetic nerve response to hypoxia in sham rabbits to a greater extent than treatment with either inhibitor alone and was without effect in CHF rabbits. In addition, using immunostaining and Western blot analyses, we found that expression of neuronal NOS, endothelial NOS, and HO-2 protein (expressed as the ratio of NOS or HO-2 expression to β-tubulin protein expression) was lower in CBs from CHF (0.19 ± 0.04, 0.17 ± 0.06, and 0.15 ± 0.02, respectively) than sham (0.63 ± 0.04, 0.56 ± 0.06, and 0.27 ± 0.03, respectively) rabbits ( P < 0.05). These results suggest that a deficiency of NO and CO in the CBs augments peripheral chemoreflex sensitivity to hypoxia in CHF.

Two patterns of daily hypoxic exposure and their effects on measures of chemosensitivity in humans

2007 ◽  
Vol 103 (6) ◽  
pp. 1973-1978 ◽  
Author(s):  
Michael S. Koehle ◽  
A. William Sheel ◽  
William K. Milsom ◽  
Donald C. McKenzie
Keyword(s):  
Oxygen Saturation ◽  
Intermittent Hypoxia ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
The Third ◽  
Long Duration ◽  
The Mean

The purpose of this study was to compare chemoresponses following two different intermittent hypoxia (IH) protocols in humans. Ten men underwent two 7-day courses of poikilocapnic IH. The long-duration IH (LDIH) protocol consisted of daily 60-min exposures to normobaric 12% O2. The short-duration IH (SDIH) protocol comprised twelve 5-min bouts of 12% O2, separated by 5-min bouts of room air, daily. Isocapnic hypoxic ventilatory response (HVR) was measured daily during the protocol and 1 and 7 days following. Hypercapnic ventilatory response (HCVR) and CO2 threshold and sensitivity (by the modified Read rebreathing technique) were measured on days 1, 8, and 14. Following 7 days of IH, the mean HVR was significantly increased from 0.47 ± 0.07 and 0.47 ± 0.08 to 0.70 ± 0.06 and 0.79 ± 0.06 l·min−1·%SaO2−1 (LDIH and SDIH, respectively), where %SaO2 is percent arterial oxygen saturation. The increase in HVR reached a plateau after the third day. One week post-IH, HVR values were unchanged from baseline. HCVR increased from 3.0 ± 0.4 to 4.0 ± 0.5 l·min−1·mmHg−1. In both the hyperoxic and hypoxic modified Read rebreathing tests, the slope of the CO2/ventilation plot was unchanged by either intervention, but the CO2/ventilation curve shifted to the left following IH. There were no correlations between the changes in response to hypoxia and hypercapnia. There were no significant differences between the two IH protocols for any measures, indicating that comparable changes in chemoreflex control occur with either protocol. These results also suggest that the two methods of measuring CO2 response are not completely concordant and that the changes in CO2 control do not correlate with the increase in the HVR.

Postnatal maturation of peripheral chemoreceptor ventilatory response to O2 and CO2 in newborn lambs

1996 ◽  
Vol 80 (6) ◽  
pp. 1928-1933 ◽  
Author(s):  
E. Canet ◽  
I. Kianicka ◽  
J. P. Praud
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Time Frame ◽  
Peripheral Chemoreceptor ◽  
Postnatal Maturation ◽  
Time Courses ◽  
End Tidal ◽  
Peripheral Chemoreflex ◽  
End Tidal Co2

Although studies on lambs have shown that carotid body sensitivity to O2 is reset postnatally, it is still unknown whether O2 and CO2 peripheral chemoreflexes undergo parallel postnatal maturation. The present study was designed to analyze maturation of O2 and CO2 peripheral chemoreflexes in 10 lambs at < 24 h and at 12 days of age. We measured the ventilatory (VE) response to three tidal breaths of pure N2 or 13% CO2 in air. Overall, the N2 peripheral chemoreflex increased significantly with maturation [VE/end-tidal O2 (ml.min-1.kg-1.Torr-1) = 2.94 +/- 0.91 at < 24 h vs. 5.13 +/- 0.59 at 12 days, P < 0.05], whereas the CO2 peripheral chemoreflex did not change (VE/end-tidal CO2 = 7.04 +/- 0.98 at < 24 h vs. 7.75 +/- 1.07 at 12 days, not significant). We conclude that the CO2 peripheral chemoreflex does not change in awake lambs within the time frame studied, in contrast to a marked postnatal maturation of the O2 peripheral chemoreflex. The different time courses of O2 and CO2 peripheral chemoreflex maturation support the concept that carotid body sensitivities to O2 and CO2 do not depend on the same basic mechanisms.

Oxygen and Effective Vascular Compliance in Acute Heart Failure

1975 ◽  
Vol 53 (3) ◽  
pp. 504-507
Author(s):  
P. Larochelle ◽  
R. I. Ogilvie
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Arterial Oxygen Tension ◽  
Arterial Oxygen ◽  
Compensatory Mechanism ◽  
Venous Bypass ◽  
Vascular Compliance ◽  
Anesthetized Dogs ◽  
Cardiac Filling ◽  
Effective Vascular Compliance

The effect of hypoxemia on total vascular compliance was studied in anesthetized dogs using a venous bypass technique. Cardiac output was kept constant with an extracorporeal pump and respiration controlled to maintain normocapnia. When nitrogen was added to the respired gas to produce an arterial [Formula: see text], total vascular compliance was rapidly and significantly reduced to 0.93 ml (mm Hg)−1 kg−1 with incomplete recovery to baseline values of 1.30 ± 0.06 ml (mm Hg)−1 kg−1 during subsequent ventilation with 100% oxygen. Acute heart failure was induced by gradual aortic constriction. Ventilation with 100% oxygen failed to prevent a gradual reduction in total vascular compliance to 0.86 ml (mm Hg)−1 kg−1 from a baseline value of 1.23 ± 0.06 ml (mm Hg)−1 kg−1. Ventilation with 100% oxygen following the reduction in vascular compliance during acute heart failure also failed to significantly alter this parameter. Thus, improvement of arterial oxygen tension in patients with acute heart failure would be beneficial in providing greater oxygen delivery to the tissues without abolishing a compensatory mechanism of reduced vascular compliance which attempts to maintain a cardiac filling gradient of pressure.

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

2020 ◽  
Author(s):  
Joshua M. Bock ◽  
Brady E. Hanson ◽  
Thomas F. Asama ◽  
Andrew J. Feider ◽  
Satoshi Hanada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Ventilatory Response ◽  
High Dose ◽  
Inorganic Nitrate ◽  
Obstructive Sleep ◽  
Chemoreflex Sensitivity ◽  
Nitrate Supplementation ◽  
High Doses ◽  
Peripheral Chemoreflex

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±10years, 29.2±5.8kg/m2, apnea-hypopnea index=17.8±8.1, 43%F) completed three visits. Resting brachial blood pressure, as well as cardiopulmonary responses to inspiratory hypoxia, were measured before, and two hours after, acute inorganic nitrate supplementation (~0.10mmol [placebo], 4.03mmol [low-dose], and 8.06mmol [high-dose]). Placebo did not increase either plasma [nitrate] (30±52 to 52±23μM, P=0.26) or [nitrite] (266±153 to 277±164nM, P=0.21); however, both increased following low-(29±17 to 175±42μM, 220±137 to 514±352nM) and high-doses (26±11 to 292±90μM, 248±155 to 738±427nM, respectively, P<0.01 for all). Following placebo, systolic blood pressure increased (120±9 to128±10mmHg, P<0.05) whereas no changes were observed following low-(121±11 to 123±8mmHg, P=0.19) or high-dose (124±13 to 124±9mmHg, P=0.96). The peak ventilatory response to hypoxia increased following placebo (3.1±1.2 to 4.4±2.6L/min, P<0.01) but not low-(4.4±2.4 to 5.4±3.4L/min, P=0.11) or high-doses (4.3±2.3 to 4.8±2.7L/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.

Effects of carotid body hypocapnia during ventilatory acclimatization to hypoxia

1997 ◽  
Vol 82 (1) ◽  
pp. 118-124 ◽  
Author(s):  
M. R. Dwinell ◽  
P. L. Janssen ◽  
J. Pizarro ◽  
G. E. Bisgard
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Control Level ◽  
Blood Gases ◽  
Initial Response ◽  
Time Dependent ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Additional Group ◽  
Ventilatory Response To Hypoxia

Dwinell, M. R., P. L. Janssen, J. Pizarro, and G. E. Bisgard. Effects of carotid body hypocapnia during ventilatory acclimatization to hypoxia. J. Appl. Physiol. 82(1): 118–124, 1997.—Hypoxic ventilatory sensitivity is increased during ventilatory acclimatization to hypoxia (VAH) in awake goats, resulting in a time-dependent increase in expired ventilation (V˙e). The objectives of this study were to determine whether the increased carotid body (CB) hypoxic sensitivity is dependent on the level of CB CO2 and whether the CB CO2 gain is changed during VAH. Studies were carried out in adult goats with CB blood gases controlled by an extracorporeal circuit while systemic (central nervous system) blood gases were regulated independently by the level of inhaled gases. Acute V˙e responses to CB hypoxia (CB [Formula: see text] 40 Torr) and CB hypercapnia (CB [Formula: see text] 50 and 60 Torr) were measured while systemic normoxia and isocapnia were maintained. CB[Formula: see text] was then lowered to 40 Torr for 4 h while the systemic blood gases were kept normoxic and normocapnic. During the 4-h CB hypoxia, V˙e increased in a time-dependent manner. Thirty minutes after return to normoxia, the ventilatory response to CB hypoxia was significantly increased compared with the initial response. The slope of the CB CO2 response was also elevated after VAH. An additional group of goats ( n = 7) was studied with a similar protocol, except that CB [Formula: see text]was lowered throughout the 4-h hypoxic exposure to prevent reflex hyperventilation. CB [Formula: see text] was progressively lowered throughout the 4-h CB hypoxic period to maintainV˙e at the control level. After the 4-h CB hypoxic exposure, the ventilatory response to hypoxia was also significantly elevated. However, the slope of the CB CO2 response was not elevated after the 4-h hypoxic exposure. These results suggest that CB sensitivity to both O2 and CO2 is increased after 4 h of CB hypoxia with systemic isocapnia. The increase in CB hypoxic sensitivity is not dependent on the level of CB CO2 maintained during the 4-h hypoxic period.

Abstract 042: Carotid Body Ablation of TRPV1 Reduces Chemoreflex Sensitivity in Rats With Heart Failure

Hypertension ◽  
2019 ◽  
Vol 74 (Suppl_1) ◽  
Author(s):  
Sharon D de Morais ◽  
Irving H Zucker ◽  
Harold D Schultz
Keyword(s):  
Heart Failure ◽  
Carotid Body ◽  
Chemoreflex Sensitivity

Attenuated carotid body hypoxic sensitivity after prolonged hypoxic exposure

1991 ◽  
Vol 70 (2) ◽  
pp. 748-755 ◽  
Author(s):  
K. Tatsumi ◽  
C. K. Pickett ◽  
J. V. Weil
Keyword(s):  
Carotid Body ◽  
Prolonged Exposure ◽  
Ventilatory Response ◽  
Barometric Pressure ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Hypoxic Ventilatory Response ◽  
End Tidal ◽  
Awake Cats ◽  
Body Response

Prolonged exposure to hypoxia is accompanied by decreased hypoxic ventilatory response (HVR), but the relative importance of peripheral and central mechanisms of this hypoxic desensitization remain unclear. To determine whether the hypoxic sensitivity of peripheral chemoreceptors decreases during chronic hypoxia, we measured ventilatory and carotid sinus nerve (CSN) responses to isocapnic hypoxia in five cats exposed to simulated altitude of 5,500 m (barometric pressure 375 Torr) for 3-4 wk. Exposure to 3-4 wk of hypobaric hypoxia produced a decrease in HVR, measured as the shape parameter A in cats both awake (from 53.9 +/- 10.1 to 14.8 +/- 1.8; P less than 0.05) and anesthetized (from 50.2 +/- 8.2 to 8.5 +/- 1.8; P less than 0.05). Sustained hypoxic exposure decreased end-tidal CO2 tension (PETCO2, 33.3 +/- 1.2 to 28.1 +/- 1.3 Torr) during room-air breathing in awake cats. To determine whether hypocapnia contributed to the observed depression in HVR, we also measured eucapnic HVR (PETCO2 33.3 +/- 0.9 Torr) and found that HVR after hypoxic exposure remained lower than preexposed value (A = 17.4 +/- 4.2 vs. 53.9 +/- 10.1 in awake cats; P less than 0.05). A control group (n = 5) was selected for hypoxic ventilatory response matched to the baseline measurements of the experimental group. The decreased HVR after hypoxic exposure was associated with a parallel decrease in the carotid body response to hypoxia (A = 20.6 +/- 4.8) compared with that of control cats (A = 46.9 +/- 6.3; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Resting Arterial Oxygen Tension Influences Pulmonary Vascular Resistance in Heart Failure

2006 ◽  
Vol 12 (6) ◽  
pp. S11
Author(s):  
Thomas P. Olson ◽  
Robert P. Frantz ◽  
Kathy A. O'Malley ◽  
Bruce D. Johnson
Keyword(s):  
Heart Failure ◽  
Pulmonary Vascular Resistance ◽  
Oxygen Tension ◽  
Vascular Resistance ◽  
Arterial Oxygen Tension ◽  
Arterial Oxygen
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