Influence of reduced carotid body drive during sustained hypoxia on hypoxic depression of ventilation in humans

1996 ◽  
Vol 81 (2) ◽  
pp. 565-572 ◽  
Author(s):  
A. Dahan ◽  
D. Ward ◽  
M. van den Elsen ◽  
J. Temp ◽  
A. Berkenbosch
Keyword(s):  
Carotid Body ◽  
Hypoxic Exposure ◽  
Hypoxic Response ◽  
Air Breathing ◽  
Carotid Bodies ◽  
Delayed Recovery ◽  
End Tidal ◽  
Second Period ◽  
Sustained Hypoxia

To evaluate whether the intact hypoxic drive from the carotid bodies during sustained hypoxia is required for the generation of hypoxic depression of ventilation (VE), 16 volunteers were exposed to two consecutive periods of isocapnic hypoxia (first period 20 min; second period 5 min; end-tidal PO2 45 Torr) separated by 6 min of normoxia. In study A, saline was given. In study B, 3 micrograms.kg-1.min-1 i.v. dopamine (DA), a carotid body inhibitor, was given during the first hypoxic exposure followed by saline during normoxia and the second hypoxic exposure. In study C, 20 min of normoxia with DA preceded 6 min of normoxia and 5 min of hypoxia without DA. The first peak hypoxic VE (PHV) in study A was approximately 100% above normoxic VE. After 20 min of hypoxia, VE declined to 60% above normoxic VE. The second PHV in study A was only 60% of the first PHV. We relate this delayed recovery from hypoxia to "ongoing" effects of hypoxic depression. During DA infusion, the changes in VE due to sustained hypoxia were insignificant (study B). The second PHV in study B was not different from the PHV after air breathing in studies A and C. This indicates that the recovery from sustained hypoxia with a suppressed carotid body drive was complete within 6 min. Our results show that despite central hypoxia the absence of ventilatory changes during 20 min of isocapnic hypoxia due to intravenous DA prevented the generation of central hypoxic depression and the depression of a subsequent hypoxic response.

Ventilatory responses to CO2 and hypoxia after sustained hypoxia in awake cats

1994 ◽  
Vol 76 (6) ◽  
pp. 2262-2266 ◽  
Author(s):  
W. Long ◽  
D. Lobchuk ◽  
N. R. Anthonisen
Keyword(s):  
Initial Response ◽  
Hypoxic Exposure ◽  
Initial Increase ◽  
Hypoxic Response ◽  
Air Breathing ◽  
Ventilatory Responses ◽  
Before And After ◽  
End Tidal ◽  
Awake Cats ◽  
Sustained Hypoxia

In humans and cats the ventilatory response to 30 min of isocapnic hypoxia is biphasic with an initial increase followed by a decrease, termed “hypoxic depression.” In humans, 30 min of hypoxia reduces the initial response to a subsequent hypoxic exposure. These experiments were to determine whether the same occurred in cats. Cats were studied while awake. End-tidal Po2 and Pco2 were measured by sampling tracheal gas, and ventilation was measured plethysmographically. In seven cats we measured ventilatory responses to two 30-min periods of isocapnic hypoxia (end-tidal Po2 = 60–65 Torr) separated by 5 min of room air breathing. The first hypoxic response was biphasic, with ventilation increasing to 149% of control at 5 min and decreasing to 117% of control at 25 min. During the second exposure, ventilation was 119% of control at 5 min and 113% of control at 25 min; 30 min of hypoxia depressed the subsequent hypoxic response. Hypoxic depression outlasted the hypoxia, suggesting that it was mediated by relatively slow neurochemical events. In five cats ventilatory responses to 5% CO2 were measured before and 5 min after 30 min of isocapnic hypoxia and before and after 30 min of room air breathing. Hypoxia did not affect CO2 responses. Thus the neurochemical events that cause hypoxic depression appear not to involve the neurons generating the response to CO2 and may be specific to those involved in the hypoxic response.

Antioxidants Reverse Reduction of the Human Hypoxic Ventilatory Response by Subanesthetic Isoflurane

2005 ◽  
Vol 102 (4) ◽  
pp. 747-753 ◽  
Author(s):  
Luc J. Teppema ◽  
Raymonda R. Romberg ◽  
Albert Dahan
Keyword(s):  
Redox State ◽  
Direct Action ◽  
Upper Airway ◽  
The Body ◽  
Alpha Tocopherol ◽  
Hypoxic Response ◽  
Carotid Bodies ◽  
Intravenous Ascorbic Acid ◽  
End Tidal ◽  
Control Sham

Background In subanesthetic concentrations, volatile anesthetics reduce the acute hypoxic response (AHR), presumably by a direct action on the carotid bodies but by an unknown molecular mechanism. To examine a possible involvement of reactive oxygen species or changes in redox state in this inhibiting effect, the authors studied the effect of antioxidants on the isoflurane-induced reduction of the AHR in humans. Methods In 10 volunteers, the authors studied the effect of antioxidants (intravenous ascorbic acid and oral alpha-tocopherol) on the reduction by isoflurane (0.12% end-tidal concentration) of the AHR on a 3-min isocapnic hypoxic stimulus (hemoglobin oxygen saturation 86 +/- 4%). All subjects participated in three separate sessions in which the effects of the antioxidants (session 1), placebo (session 2), and sham isoflurane plus antioxidants (session 3) were tested on the (sham) isoflurane-induced effect on the AHR. Results Isoflurane reduced the acute hypoxic response from 0.82 +/- 0.41 l . min . % to 0.49 +/- 0.23 l . min . % and from 0.89 +/- 0.43 l . min . % to 0.48 +/- 0.28 l . min . % in sessions 1 and 2, respectively (mean +/- SD; P < 0.05 vs. control). This reduction of the AHR was completely reversed by antioxidants (AHR = 0.76 +/- 0.39 l . min . %; not significantly different from control, session 1) but not by placebo in session 2 (AHR = 0.50 +/- 0.30 l . min . %; P < 005 vs. control). Sham isoflurane or antioxidants per se had no effect on the hypoxic response. Conclusions The data indicate that isoflurane may depress the AHR by influencing the redox state of oxygen-sensing elements in the carotid bodies. This finding may have clinical implications for patients who are prone to recurrent hypoxic episodes, e.g., due to upper airway obstruction, in the postoperative period when low-dose isoflurane may persist in the body for some time.

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)

Selected Contribution: Acute and sustained ventilatory responses to hypoxia in high-altitude natives living at sea level

2003 ◽  
Vol 94 (3) ◽  
pp. 1255-1262 ◽  
Author(s):  
Alfredo Gamboa ◽  
Fabiola León-Velarde ◽  
Maria Rivera-Ch ◽  
Jose-Antonio Palacios ◽  
Timothy R. Pragnell ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Altitude ◽  
Sea Level ◽  
Hypoxic Exposure ◽  
Ventilatory Responses ◽  
High Altitude Natives ◽  
Ventilatory Depression ◽  
End Tidal ◽  
Sustained Hypoxia

High-altitude (HA) natives have blunted ventilatory responses to hypoxia (HVR), but studies differ as to whether this blunting is lost when HA natives migrate to live at sea level (SL), possibly because HVR has been assessed with different durations of hypoxic exposure (acute vs. sustained). To investigate this, 50 HA natives (>3,500 m, for >20 yr) now resident at SL were compared with 50 SL natives as controls. Isocapnic HVR was assessed by using two protocols: protocol 1, progressive stepwise induction of hypoxia over 5–6 min; and protocol 2, sustained (20-min) hypoxia (end-tidal Po 2 = 50 Torr). Acute HVR was assessed from both protocols, and sustained HVR from protocol 2. For HA natives, acute HVR was 79% [95% confidence interval (CI): 52–106%, P = not significant] of SL controls for protocol 1 and 74% (95% CI: 52–96%, P < 0.05) for protocol 2. By contrast, sustained HVR after 20-min hypoxia was only 30% (95% CI: −7–67%, P < 0.001) of SL control values. The persistent blunting of HVR of HA natives resident at SL is substantially less to acute than to sustained hypoxia, when hypoxic ventilatory depression can develop.

Carotid chemoreceptor activity during acute and sustained hypoxia in goats

1988 ◽  
Vol 65 (4) ◽  
pp. 1796-1802 ◽  
Author(s):  
A. M. Nielsen ◽  
G. E. Bisgard ◽  
E. H. Vidruk
Keyword(s):  
Carotid Body ◽  
Discharge Frequency ◽  
Hypoxic Exposure ◽  
Arterial Pco2 ◽  
Afferent Discharge ◽  
Carotid Body Chemoreceptors ◽  
Arterial Po2 ◽  
Sustained Hypoxia ◽  
Related Increase

The role of carotid body chemoreceptors in ventilatory acclimatization to hypoxia, i.e., the progressive, time-dependent increase in ventilation during the first several hours or days of hypoxic exposure, is not well understood. The purpose of this investigation was to characterize the effects of acute and prolonged (up to 4 h) hypoxia on carotid body chemoreceptor discharge frequency in anesthetized goats. The goat was chosen for study because of its well-documented and rapid acclimatization to hypoxia. The response of the goat carotid body to acute progressive isocapnic hypoxia was similar to other species, i.e., a hyperbolic increase in discharge as arterial PO2 (PaO2) decreased. The response of 35 single chemoreceptor fibers to an isocapnic [arterial PCO2 (PaCO2) 38-40 Torr)] decrease in PaO2 of from 100 +/- 1.7 to 40.7 +/- 0.5 (SE) Torr was an increase in mean discharge frequency from 1.7 +/- 0.2 to 5.8 +/- 0.4 impulses. During sustained isocapnic steady-state hypoxia (PaO2 39.8 +/- 0.5 Torr, PaCO2, 38.4 +/- 0.4 Torr) chemoreceptor afferent discharge frequency remained constant for the first hour of hypoxic exposure. Thereafter, single-fiber chemoreceptor afferents exhibited a progressive, time-related increase in discharge (1.3 +/- 0.2 impulses.s-1.h-1, P less than 0.01) during sustained hypoxia of up to 4-h duration. These data suggest that increased carotid chemoreceptor activity contributes to ventilatory acclimatization to hypoxia.

Sustained hypoxia-induced proliferation of carotid body type I cells in rats

2008 ◽  
Vol 104 (3) ◽  
pp. 803-808 ◽  
Author(s):  
Z.-Y. Wang ◽  
E. B. Olson ◽  
D. E. Bjorling ◽  
G. S. Mitchell ◽  
G. E. Bisgard
Keyword(s):  
Cell Proliferation ◽  
Carotid Body ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hypoxic Exposure ◽  
Type I ◽  
Body Type ◽  
Cellular Changes ◽  
And Function ◽  
I Cells ◽  
Sustained Hypoxia

Sustained hypoxia (SH) has been shown to cause profound morphological and cellular changes in carotid body (CB). However, results regarding whether SH causes CB type I cell proliferation are conflicting. By using bromodeoxyuridine, a uridine analog that is stably incorporated into cells undergoing DNA synthesis, we have found that SH causes the type I cell proliferation in the CB; the proliferation occurs mainly during the first 1–3 days of hypoxic exposure. Moreover, the new cells survive for at least 1 mo after the return to normoxia. Also, SH does not cause any cell death in CB as examined by the terminal deoxynucleotidyl transferase-mediated dUTP-X nick-end labeling assay. Taken together, our results suggest that SH stimulates CB type I cell proliferation, which may produce long-lasting changes in CB morphology and function.

Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans

1990 ◽  
Vol 69 (3) ◽  
pp. 1159-1164 ◽  
Author(s):  
D. Georgopoulos ◽  
Z. Bshouty ◽  
M. Younes ◽  
N. R. Anthonisen
Keyword(s):  
Acute Hypoxia ◽  
Periodic Breathing ◽  
Hypoxic Exposure ◽  
Chemical Stimulus ◽  
Hypoxic Environment ◽  
Normal Humans ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Sustained Hypoxia

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.

Effects of CO2 breathing on ventilatory response to sustained hypoxia in normal adults

1989 ◽  
Vol 66 (3) ◽  
pp. 1071-1078 ◽  
Author(s):  
D. Georgopoulos ◽  
D. Berezanski ◽  
N. R. Anthonisen
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Inhibitory Effect ◽  
Hypoxic Exposure ◽  
Initial Increase ◽  
Co2 Levels ◽  
End Tidal ◽  
The Relationship ◽  
Sustained Hypoxia ◽  
Ventilatory Response To Co2

The relationship between CO2 and ventilatory response to sustained hypoxia was examined in nine normal young adults. At three different levels of end-tidal partial pressure of CO2 (PETCO2, approximately 35, 41.8, and 44.3 Torr), isocapnic hypoxia was induced for 25 min and after 7 min of breathing 21% O2, isocapnic hypoxia was reinduced for 5 min. Regardless of PETCO2 levels, the ventilatory response to sustained hypoxia was biphasic, characterized by an initial increase (acute hypoxic response, AHR), followed by a decline (hypoxic depression). The biphasic response pattern was due to alteration in tidal volume, which at all CO2 levels decreased significantly (P less than 0.05), without a significant change in breathing frequency. The magnitude of the hypoxic depression, independent of CO2, correlated significantly (r = 0.78, P less than 0.001) with the AHR, but not with the ventilatory response to CO2. The decline of minute ventilation was not significantly affected by PETCO2 [averaged 2.3 +/- 0.6, 3.8 +/- 1.3, and 4.5 +/- 2.2 (SE) 1/min for PETCO2 35, 41.8, and 44.3 Torr, respectively]. This decay was significant for PETCO2 35 and 41.8 Torr but not for 44.3 Torr. The second exposure to hypoxia failed to elicit the same AHR as the first exposure; at all CO2 levels the AHR was significantly greater (P less than 0.05) during the first hypoxic exposure than during the second. We conclude that hypoxia exhibits a long-lasting inhibitory effect on ventilation that is independent of CO2, at least in the range of PETCO2 studied, but is related to hypoxic ventilatory sensitivity.

Recovery of the ventilatory response to hypoxia in normal adults

1988 ◽  
Vol 64 (2) ◽  
pp. 521-528 ◽  
Author(s):  
P. A. Easton ◽  
L. J. Slykerman ◽  
N. R. Anthonisen
Keyword(s):  
Young Adults ◽  
Ventilatory Response ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
Air Breathing ◽  
Arterial Blood ◽  
Complete Reversal ◽  
Sustained Hypoxia ◽  
Normal Adults ◽  
Ventilatory Response To Hypoxia

Recovery of the initial ventilatory response to hypoxia was examined after the ventilatory response had declined during sustained hypoxia. Normal young adults were exposed to two consecutive 25-min periods of sustained isocapnic hypoxia (80% O2 saturation in arterial blood), separated by varying interludes of room air breathing or an increased inspired O2 fraction (FIO2). The decline in the hypoxic ventilatory response during the 1st 25 min of hypoxia was not restored after a 7-min interlude of room air breathing; inspired ventilation (VI) at the end of the first hypoxic period was not different from VI at the beginning and end of the second hypoxic period. After a 15-min interlude of room air breathing, the hypoxic ventilatory response had begun to recover. With a 60-min interlude of room air breathing, recovery was complete; VI during the second hypoxic exposure matched VI during the first hypoxic period. Ventilatory recovery was accelerated by breathing supplemental O2. With a 15-min interlude of 0.3 FIO2 or 7 min of 1.0 FIO2, VI of the first and second hypoxic periods were equivalent. Both the decline and recovery of the hypoxic ventilatory response were related to alterations in tidal volume and mean inspiratory flow (VT/TI), with little alteration in respiratory timing. We conclude that the mechanism of the decline in the ventilatory response with sustained hypoxia may require up to 1 h for complete reversal and that the restoration is O2 sensitive.

Fine Structure of Carotid Body: Normal and Anoxic Cats

1967 ◽  
Vol 25 ◽  
pp. 150-151
Author(s):  
Fadhil Al-Lami ◽  
R.G. Murray
Keyword(s):  
Fine Structure ◽  
Adrenal Medulla ◽  
Carotid Body ◽  
Uranyl Acetate ◽  
Lead Citrate ◽  
Glomus Cells ◽  
Sustentacular Cells ◽  
Carotid Bodies

Although the fine structure of the carotid body has been described in several recent reports, uncertainties remain, and the morphological effects of anoxia on the carotid body cells of the cat have never been reported. We have, therefore, studied the fine structure of the carotid body both in normal and severely anoxic cats, and to test the specificity of the effects, have compared them with the effects on adrenal medulla, kidney, and liver of the same animals. Carotid bodies of 50 normal and 15 severely anoxic cats (9% oxygen in nitrogen) were studied. Glutaraldehyde followed by OsO4 fixations, Epon 812 embedding, and uranyl acetate and lead citrate staining, were the technics employed.We have called the two types of glomus cells enclosed and enclosing cells. They correspond to those previously designated as chemoreceptor and sustentacular cells respectively (1). The enclosed cells forming the vast majority, are irregular in shape with many processes and occasional peripheral densities (Fig. 1).

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