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.

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.

Intermittent hypoxia increases ventilation and SaO2 during hypoxic exercise and hypoxic chemosensitivity

2001 ◽  
Vol 90 (4) ◽  
pp. 1431-1440 ◽  
Author(s):  
Keisho Katayama ◽  
Yasutake Sato ◽  
Yoshifumi Morotome ◽  
Norihiro Shima ◽  
Koji Ishida ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Submaximal Exercise ◽  
Arterial Oxygen ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Equivalent ◽  
Hypoxic Exercise

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (SaO2 ) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and SaO2 during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (V˙o 2), expired minute ventilation (V˙e), and SaO2 were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2(V˙e/V˙o 2) and SaO2 during submaximal exercise. There were significant correlations among the changes in HVR at rest and inV˙e/V˙o 2 and SaO2 during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.

Hypoxic Arousal Responses in Normal Infants

PEDIATRICS ◽  
1992 ◽  
Vol 89 (5) ◽  
pp. 860-864 ◽  
Author(s):  
Sally L. Davidson Ward ◽  
Daisy B. Bautista ◽  
Thomas C. Keens
Keyword(s):  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Periodic Breathing ◽  
High Risk Group ◽  
Arterial Oxygen ◽  
Sudden Infant ◽  
Hypoxic Ventilatory Response ◽  
Quiet Sleep ◽  
Term Infants ◽  
Increased Risk

Failure to arouse in response to hypoxia has been described in infants at increased risk for sudden infant death syndrome (SIDS) and has been suggested as a possible mechanism for SIDS. However, most SIDS victims are not in a high-risk group before death. Thus, if a hypoxic arousal disorder is an important contributor to SIDS, normal infants might fail to arouse from sleep in response to hypoxia. To test this hypothesis, the authors studied hypoxic arousal responses in 18 healthy term infants younger than 7 months of age (age 12.1 ± 1.7 [SEM] weeks; 56% girls). Hypoxic arousal challenges were performed during quiet sleep by rapidly decreasing inspired oxygen tension (Pio2) to 80 mm Hg for 3 minutes or until arousal (eye opening, agitation, and crying) occurred. Tests were performed in duplicate when possible. Only 8 infants (44%) aroused in response to one or more hypoxic challenges; arousal occurred during 8 (32%) of 25 trials. There were no significant differences in lowest Pio2 or arterial oxygen saturation during hypoxia between those infants who aroused and those who failed to arouse. All 18 infants had a fall in their end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response despite failure to arouse in the majority. Periodic breathing occurred following hypoxia in only 1 (13%) of the 8 trials that resulted in arousal, compared with 16 (94%) of 17 trials without arousal (P < .005). It is concluded that the majority of normal infants younger than 7 months of age fail to arouse from quiet sleep in response to hypoxia, despite the apparent presence of a hypoxic ventilatory response.

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.

Sea-level PCO2 relates to ventilatory acclimatization at 4,300 m

1993 ◽  
Vol 75 (3) ◽  
pp. 1117-1122 ◽  
Author(s):  
J. T. Reeves ◽  
R. E. McCullough ◽  
L. G. Moore ◽  
A. Cymerman ◽  
J. V. Weil
Keyword(s):  
Sea Level ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Barometric Pressure ◽  
Interindividual Variation ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Wide Range ◽  
Time Required ◽  
End Tidal

There is considerable variation among individuals in the extent of, and the time required for, ventilatory acclimatization to altitude. Factors related to this variation are unclear. The present study tested whether interindividual variation in preascent ventilation or magnitude of hypoxic ventilatory response related to ventilatory acclimatization to altitude. Measurements in 37 healthy resting male subjects at sea level indicated a wide range (34–48 Torr) of end-tidal PCO2 values. When these subjects were taken to Pikes Peak, CO (4,300 m, barometric pressure 462 mmHg), the end-tidal PCO2 values measured on arrival and repeatedly over 19 days were correlated with the sea-level end-tidal PCO2. At 4,300 m, subjects with high end-tidal PCO2 had low values of arterial oxygen saturation (SaO2). Also, sea-level end-tidal PCO2 related to SaO2 after 19 days at 4,300 m. Twenty-six of the subjects had measurements of isocapnic hypoxic ventilatory response (HVR) at sea level. The end-tidal PCO2 values on arrival and after 19 days residence at 4,300 m were inversely related to the sea-level HVR values. Thus both the PCO2 and the HVR as measured at sea level related to the extent of subsequent ventilatory acclimatization (decrease in end-tidal PCO2) and the level of oxygenation at altitude. The finding in our cohort of subjects that sea-level end-tidal PCO2 was inversely related to HVR raised the possibility that among individuals the magnitude of the hypoxic drive to breathe influenced the amount of ventilation at all altitudes, including sea level.

Control of breathing in Sherpas at low and high altitude

1980 ◽  
Vol 49 (3) ◽  
pp. 374-379 ◽  
Author(s):  
P. H. Hackett ◽  
J. T. Reeves ◽  
C. D. Reeves ◽  
R. F. Grover ◽  
D. Rennie
Keyword(s):  
High Altitude ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Carbon Dioxide Tension ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Oxygen Administration ◽  
End Tidal

Sherpas are well known for their physical performance at extreme altitudes, yet they are reported to have blunted ventilatory responses to acute hypoxia and relative hypoventilation in chronic hypoxia. To examine this paradox, we studied ventilatory control in Sherpas in comparison to that in Westerners at both low and high altitude. At low altitude, 25 Sherpas had higher minute ventilation, higher respiratory frequency, and lower end-tidal carbon dioxide tension than 25 Westerners. The hypoxic ventilatory response of Sherpas was found to be similar to that in Westerners, even though long altitude exposure had blunted the responses of some Sherpas. At high altitude, Sherpas again had higher minute ventilation and a tendency toward higher arterial oxygen saturation than Westerners. Oxygen administration increased ventilation further in Sherpas but decreased ventilation in Westerners. We conclude that Sherpas differ from other high-altitude natives; their hypoxic ventilatory response is not blunted, and they exhibit relative hyperventilation.

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)

Increased carotid body hypoxic sensitivity during acclimatization to hypobaric hypoxia

1987 ◽  
Vol 63 (6) ◽  
pp. 2403-2410 ◽  
Author(s):  
M. Vizek ◽  
C. K. Pickett ◽  
J. V. Weil
Keyword(s):  
Carotid Body ◽  
Hypobaric Hypoxia ◽  
Shape Parameter ◽  
Carotid Sinus ◽  
Ventilatory Response ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Hypoxic Ventilatory Response ◽  
Carotid Sinus Nerve ◽  
Peripheral Chemoreceptor

Mechanisms of ventilatory acclimatization to chronic hypoxia remain unclear. To determine whether the sensitivity of peripheral chemoreceptors to hypoxia increases during acclimatization, we measured ventilatory and carotid sinus nerve responses to isocapnic hypoxia in seven cats exposed to simulated altitude of 15,000 ft (barometric pressure = 440 Torr) for 48 h. A control group (n = 7) was selected for hypoxic ventilatory responses matched to the preacclimatized measurements of the experimental group. Exposure to 48 h of hypobaric hypoxia produced acclimatization manifested as decrease in end-tidal PCO2 (PETCO2) in normoxia (34.5 +/- 0.9 Torr before, 28.9 +/- 1.2 after the exposure) as well as in hypoxia (28.1 +/- 1.9 Torr before, 21.8 +/- 1.9 after). Acclimatization produced an increase in hypoxic ventilatory response, measured as the shape parameter A (24.9 +/- 2.6 before, 35.2 +/- 5.6 after; P less than 0.05), whereas values in controls remained unchanged (25.7 +/- 3.2 and 23.1 +/- 2.7; NS). Hypoxic exposure was associated with an increase in the carotid body response to hypoxia, similarly measured as the shape parameter A (24.2 +/- 4.7 in control, 44.5 +/- 8.2 in acclimatized cats). We also found an increased dependency of ventilation on carotid body function (PETCO2 increased after unilateral section of carotid sinus nerve in acclimatized but not in control animals). These results suggest that acclimatization is associated with increased hypoxic ventilatory response accompanied by enhanced peripheral chemoreceptor responsiveness, which may contribute to the attendant rise in ventilation.

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.

scholarly journals The hypoxic ventilatory response and ventilatory long-term facilitation are altered by time of day and repeated daily exposure to intermittent hypoxia

2011 ◽  
Vol 110 (1) ◽  
pp. 15-28 ◽  
Author(s):  
David G. Gerst ◽  
Sanar S. Yokhana ◽  
Laura M. Carney ◽  
Dorothy S. Lee ◽  
M. Safwan Badr ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Time Of Day ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Daily Exposure ◽  
Long Term Facilitation

This study examined whether time of day and repeated exposure to intermittent hypoxia have an impact on the hypoxic ventilatory response (HVR) and ventilatory long-term facilitation (vLTF). Thirteen participants with sleep apnea were exposed to twelve 4-min episodes of isocapnic hypoxia followed by a 30-min recovery period each day for 10 days. On days 1 (initial day) and 10 (final day) participants completed the protocol in the evening (PM); on the remaining days the protocol was completed in the morning (AM). The HVR was increased in the morning compared with evening on the initial (AM 0.83 ± 0.08 vs. PM 0.64 ± 0.11 l·min−1·%SaO2−1; P ≤ 0.01) and final days (AM 1.0 ± 0.08 vs. PM 0.81 ± 0.09 l·min−1·%SaO2−1; P ≤ 0.01, where %SaO2 refers to percent arterial oxygen saturation). Moreover, the magnitude of the HVR was enhanced following daily exposure to intermittent hypoxia in the morning (initial day 0.83 ± 0.08 vs. final day 1.0 ± 0.08 l·min−1·%SaO2−1; P ≤ 0.03) and evening (initial day 0.64 ± 0.11 vs. final day 0.81 ± 0.09 l·min−1·%SaO2−1; P ≤ 0.03). vLTF was reduced in the morning compared with the evening on the initial (AM 19.03 ± 0.35 vs. PM 22.30 ± 0.49 l/min; P ≤ 0.001) and final (AM 20.54 ± 0.32 vs. PM 23.11 ± 0.54 l/min; P ≤ 0.01) days. Following daily exposure to intermittent hypoxia, vLTF was enhanced in the morning (initial day 19.03 ± 0.35 vs. final day 20.54 ± 0.32 l/min; P ≤ 0.01). We conclude that the HVR is increased while vLTF is decreased in the morning compared with the evening in individuals with sleep apnea and that the magnitudes of these phenomena are enhanced following daily exposure to intermittent hypoxia.

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